Biomedical subjects

N Grunnet

Publications and source records attributed to N Grunnet.

At least 37 records · Page 2Linked to original sources

PubMed1998

Leukocyte filtration does not affect lymphocyte subpopulations and NK cell function in recipients of blood transfusions.

BACKGROUND AND OBJECTIVES: The possible immunosuppressive action of blood transfusion has aroused great interest recently, particularly with respect to its effects on tumor growth and recurrence rate of malignant disease. MATERIALS AND METHODS: The effect of blood transfusion on lymphocyte subpopulations and NK cell function preoperatively and 6 months postoperatively was studied in 129 patients treated with elective surgery for colorectal malignancy. Forty-two patients (33%) received blood transfusions, 21 of them randomly allocated to receive leukocyte-depleted blood products. Investigation was by means of conventional laboratory methods. RESULTS: In 21 patients receiving a median of 3 units of non-leukocyte-depleted blood products (NLD), a significant reduction in CD4+ lymphocytes (44% vs. 40%, p < 0.01) occurred. In contrast, no significant changes in CD4+ lymphocytes were observed in the 21 patients transfused with leukocyte-depleted blood products (LD). However, with respect to lymphocyte subpopulations and NK cell function, differences between the NLD and LD groups were not significant. There was a marginal decrease in HLA-DR+ lymphocytes in the NLD patients without a history of previous transfusion. CONCLUSIONS: There seems to be no major change in lymphocyte subpopulations and NK cell function 6 months after blood transfusion. Thus we cannot confirm our previous findings of a reduced number of CD20+ cells after blood transfusion.

Aged↗

PubMed1997

Chemotaxis and IL-8 receptor expression in B cells from normal and HIV-infected subjects.

To date, the activities of the alpha chemokines for human peripheral B cells from normal subjects (N-B cells) or from HIV-infected subjects (HIV-B cells) are not well established. No report on the IL-8R expression on N-B cells and HIV-B cells has been seen. We report in this work that the alpha chemokines IL-8 and growth-regulatory oncogene-alpha (GRO-alpha) induce a chemotactic migration of N-B cells and HIV-B cells via stimulating the IL-8RB on these cells. The chemotaxis of N-B cells can be inhibited by IFN-gamma and IL-2, and augmented by IL-4 and IL-13, whereas TNF-alpha and IL-10 have no influence. The chemotaxis of HIV-B cells can be inhibited by IFN-gamma and IL-2, and augmented by TNF-alpha, IL-4, and IL-10, whereas IL-13 has no influence. IL-8R are expressed more abundantly on freshly isolated HIV-B cells than N-B cells (51% and 15%, respectively). The IL-8R on N-B cells can be down-regulated by IFN-gamma, IL-2, and TNF-alpha (selectively on IL-8RA), and up-regulated by IL-4 and IL-13, whereas IL-10 has no influence. The IL-8R on HIV-B cells can be down-regulated by IFN-gamma and IL-2, and up-regulated by TNF-alpha, IL-4, and IL-10, whereas IL-13 has no influence. Importantly, N-B cell and HIV-B cell chemotaxis toward IL-8 and GRO-alpha can be blocked by anti-IL-8RB polyclonal Ab, but not by anti-IL-8RA polyclonal Ab. Our results demonstrate that IL-8 and GRO-alpha are important inflammatory mediators that stimulate the directional migration and recruitment of B lymphocytes. The migratory behavior and the expression of IL-8R on HIV-B cells and some of the reactions to Th1- and Th2-like cytokines are modified significantly during HIV infection.

Adult↗

PubMed1997

Report from the HLA class II typing by PCR-SSP Multicentre Study.

Results from 360 HLA-DR and -DQ 'low-resolution' typings with polymerase chain reaction sequence-specific primers (PCR-SSP), performed by nine laboratories, were analysed for their overall utility in routinely defining the HLA-DR1-DR18, DR51-DR53 and DQ1-DQ9 specificities in less than 2.5 h. Thirty EDTA blood samples and 10 DNA samples were distributed and analysed by each laboratory. DNA was extracted using a rapid bromide salt extraction protocol. Complete HLA-DR and -DQ typings were performed, three by three, on pre-aliquoted 96-tube PCR trays. When compared with reference typing, 351/360 (98%) correct DR typings were obtained, whereas 320/360 (89%) of the DQ phenotypes were correctly assigned. The time for three complete HLA-DR and -DQ 'low-resolution' typings, including DNA extraction, ranged from 2.0 h to 2.3 h. Unfortunately, an unusually high level of PCR amplification failures was observed (3%), probably due to diffusion and a significant volume loss from some of the pre-aliquoted primer mixes. Consequently, only 52% of the typings were without any amplification failure, and 0-2 amplification failures where found in 88% of the PCR-SSP typings performed. The number of HLA-DR-DQ retypings needed was 7 and 8%, respectively, reflecting the low number of typings where allelic identification was directly affected by the relatively high level of amplification failures in this study. Thus, a 91-98% success rate of correctly identified HLA-DR and -DQ alleles could be maintained, even under suboptimal typing conditions.

Alleles↗

PubMed1997

HLA-B27 polymorphism and worldwide susceptibility to ankylosing spondylitis.

HLA-B27 is strongly associated to ankylosing spondylitis (AS) and represents a family of eleven B27 alleles (B*2701-11). Our aim was to analyze the distribution of B27 subtypes by PCR/SSOP and genomic sequencing in a large group of populations (n = 17). 711 B27-positive samples from Caucasoid, Asian, African, Amerindian and Polynesian populations were selected to ascertain transracial gene mapping of the B27 subtypes. 476 of these were AS patients, chosen to investigate the contribution of B27 alleles to AS susceptibility. Some significant new findings have arisen from this study: 1) B*2705 was the predominant subtype in circumpolar and subarctic areas. B*2702 was found to be practically restricted to Caucasian populations, showing a higher frequency in Middle-East (Jews) and North Africa (Arabs/Berbers) groups. 2) B*2703 appears associated with AS in Western Africans. This is of remarkable interest since it was suggested that B*2703 would be negatively disease-associated. 3) Although B*2706 appears negatively associated with AS in Thais, we identified two patients from northern China carrying it. This may be a reflection of a disease heterogeneity and could indicate that more than one pathogenic agent can be involved in AS. B*2709 has been recently described as negatively associated with AS in Sardinians. The molecular changes His114Asp (B*2706) and Asp116His (B*2709) could modify the genetic susceptibility to AS.

Alleles↗

PubMed1997

Frequency of HLA-B27 subtypes in a Danish population and in Danish patients with ankylosing spondylitis.

Polymerase chain reaction in combination with sequence-specific oligonucleotide probes were used to analyze nine HLA-B27 subtypes among 51 healthy HLA-B27 positive Danish blood donors and 30 Danish HLA-B27 positive patients with ankylosing spondylitis (AS). In the group of healthy Danes we found two subtypes, B*2705 (90.2%) and B*2702 (9.8%), however, among the AS patients only the B*2705 subtype was detected. We did not find a significant evidence for associations between AS and a particular HLA-B27 subtype in a Danish population.

Denmark↗

PubMed1996

Influence of Lewis alpha1-3/4-L-fucosyltransferase (FUT3) gene mutations on enzyme activity, erythrocyte phenotyping, and circulating tumor marker sialyl-Lewis a levels.

Fucosylated glycoproteins carrying alpha1-4 fucose residues are of importance for cell adhesion and as tumor markers. The Lewis gene, FUT3, encodes the only known alpha1-4-fucosyltransferase (FucT), and individuals who are deficient in this enzyme type as Lewis-negative on erythrocytes. We examined the mutational spectrum of the Lewis gene in Denmark and found 6 different mutations. Five, T59G, T202C, C314T, G508A, and T1067A, were frequent, and one, C445A, was only detected in one out of 40 individuals. Allele-specific polymerase chain reaction as well as cloning of FUT3 alleles showed that the 202 and 314 mutations were co-located on the same allele. COS7 cells transfected with an allele having the 202/314 mutations lacked enzyme activity. Polymerase chain reaction-cleavage assays were established for the genotyping of healthy individuals as well as 20 genuine Lewis-negative cancer patients and 10 non-genuine. The latter have Lewis-negative erythrocytes but saliva alpha1-4FucT activity. The genuine Lewis-negative individuals had mutations on both FUT3 alleles. In 66 healthy individuals, a gene dosage effect was detected as FUT3 heterozygous individuals had a lower alpha1-4FucT activity in saliva than did homozygous wild-type individuals. The lower enzyme level in heterozygous individuals resulted in a significantly (p < 0.04) lower level of circulating sialyl-Lewis a structure in serum. This has the clinical impact that cut-off levels in tumor marker assays should be defined on the basis of genotyping. In the group of non-genuine Lewis-negative cancer patients, whose erythrocytes convert from Lewis-positive to Lewis-negative during the disease, FUT3 heterozygosity was significantly (p < 0.05) more common.

ABO Blood-Group System↗

PubMed1996

[Epidermodysplasia verruciformis, human Papillomavirus infection, genital epithelial neoplasia and possible immunodeficiency].

Papilloma virus infections are common in patients with immune defect/suppression. We describe a case of regional localised epidermodysplasia verruciformis in combination with genital intraepithelial neoplasia, refractory anaemia, and impaired immunity as demonstrated by lymphopenia with reduced B-cell/T-cell ratio, but normal T-helper/T-suppressor (CD4/CD8) ratio, and neutrophils with reduced spontaneous migration and chemotaxis. The regional localisation of the lesion and the changes in the cell mediated immunity are not classical for epidermodysplasia verruciformis. It is concluded that an increased tendency to papilloma virus infections and/or intraepithelial neoplasia should alert the clinician to the possibility of an immune defect.

Adult↗

PubMed1996

Short-term changes in the immune system of elite swimmers under competition conditions. Different immunomodulation induced by various types of sport.

This study was designed to investigate changes in the immune system of elite swimmers compared with well-conditioned age- and sex-matched controls in relation to a competition swim (field study). Furthermore, the aim was to reveal possible differences in immune system changes depending on the type of sport performed by comparing with an earlier study of similar design, from the same laboratory that tested elite runners in relation to a competition run. The swimmers were tested before, immediately after and 2 h and 24 h after a competition swim. Lymphocyte subsets (CD5, CD3, HLA-DR, CD4, CD8, CD19, CD3/CD16+56, CD57, CD18, CD16/CD122) all increased after the run, decreased to normal or subnormal levels after 2 h, and returned to normal after 24 h (absolute numbers). The findings were identical for the swimmers and the age- and sex-matched control group. No change in polymorphonuclear granulocyte migration was found. The lymphocyte proliferative responses decreased 2 h after the exercise. No changes were seen in plasma cytokine levels (interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) in relation to exercise, but significantly lower baseline values for IL-6 were observed in the swimmers. An increase in total natural killer cell activity immediately after exercise, followed after 2 h by a decrease, was seen in both swimmers and controls. Finally, no complement activation was detected. Compared with an earlier study of elite runners, differences were seen in granulocyte chemotactic response, TNF-alpha plasma activity and the lymphocyte proliferative response to mitogen. These differences might be explained by the degree of immune system activation following muscle damage during exercise, inducing an increase in cytokines, which are known to activate and modulate both lymphocytes and granulocyte function. Our findings demonstrate identical exercise-induced, immune system changes in elite swimmers and well conditioned controls, and furthermore, the findings suggest that different types of sport performed at maximum intensity induce different immune system changes.

Adolescent↗

PubMed1996

Maternal HLA class II alleles predispose to pregnancy losses in Danish women with recurrent spontaneous abortions and their female relatives.

PROBLEM: If damage to the trophoblast mediated through autoimmune mechanisms is responsible for recurrent spontaneous abortions (RSA), maternal class II HLA antigens might be expected to be involved. We wanted to evaluate the impact of these antigens on pregnancy outcome in RSA women and their relatives. METHOD: HLA-DR and -DQ typing using RFLP and PCR-SSP methods was carried out in 234 Danish women with unexplained RSA and 360 controls. The HLA-DR types were correlated to outcome of the next pregnancy in 94 patients. Sisters, brothers, and wives of brothers of 146 consecutive patients were HLA typed and their pregnancy outcomes were correlated to the HLA-DR types. RESULTS: HLA-DR1/Br and -DR3 were each significantly increased in women with at least four previous pregnancy losses (both P-values < 0.05 after correction for multiple comparisons). In the prospective study, 62% of the HLA-DR1/Br and/or -DR3 positive patients miscarried the next pregnancy compared with only 29% of those negative for both allogenotypes (P = 0.025). The family studies indicated that female relatives of RSA patients had a greater risk (odds ratio = 5.0, 95% CI = 2.0-11.0) of pregnancy losses when positive for HLA-DR1/Br and/or -DR3 than those negative for the allogenotypes. CONCLUSIONS: Maternal HLA-DR allogenotypes DR1/Br and -DR3 or closely linked genes seem to predispose to pregnancy losses in RSA patients and their first degree relatives.

Abortion, Habitual↗

PubMed1995

[Use of rheumatoid factor IgM analysis. A questionnaire study among the users].

The aim of this study was to describe who orders the rheumatoid factor analysis (RF-IgM) and the clinical indication compared to the result of the analysis. All analyses over a one month period were registered. The doctor who had ordered the analysis was contacted in order to answer a questionnaire asking about the clinical symptoms, results of other analyses and whether this analysis were the first or more. Four hundred and sixty-seven analyses were registered (population: about 300,000), 21% with a positive ELISA result (cut-off: 6 IU/ml). Thirty-one percent of the patients had clinical symptoms associated with rheumatoid arthritis. Sixty-seven percent of the analyses were ordered by the general practitioner. If we changed the cut-off to 15 or 20 IU/ml only 14 or 12 analyses were registered as having a positive result. We conclude that the analysis is often used for case-finding, perhaps the frequency could be reduced if the analysis were used more specifically and that the doctor who receives the answer has to be aware of the influence of the cut-off used by the local laboratory.

Adult↗

PubMed1995

Cost-effectiveness of blood transfusion and white cell reduction in elective colorectal surgery.

BACKGROUND: The use of white cell (WBC)-reduced blood in elective colorectal surgery appears to reduce the frequency of postoperative infection. The question to be addressed is whether the cost:benefit ratio justifies the recommendation that WBC-reduced blood should be used for all colorectal surgery. STUDY DESIGN AND METHODS: Patients admitted for elective colorectal surgery (n = 197) were randomly assigned to receive transfusion consisting of whole blood or WBC-reduced whole blood. Postoperative complications, postoperative stay, and hospital charges were compared. RESULTS: Forty-eight patients received WBC-reduced whole blood, 56 received unfiltered whole blood, and 93 received no transfusion. Postoperative infections were significantly higher (p < 0.001) in the group that received unfiltered whole blood. That group also had longer hospital stays: 17 days as compared to stays of 10 and 11 days for the group receiving no transfusion and the group receiving filtered whole blood transfusions, respectively (p < 0.01). The total hospital cost per patient receiving unfiltered whole blood was $12,347, as compared to $7,867 for those who received WBC-reduced whole blood and $7,030 for those who received no transfusion. CONCLUSION: The use of WBC-reduced whole blood transfusions in elective colorectal surgery significantly reduces the frequency of postoperative infection, the length of hospital stay, and the total hospital charges for patients needing blood transfusion.

Adult↗

PubMed1995

Placebo-controlled trial of treatment of unexplained secondary recurrent spontaneous abortions and recurrent late spontaneous abortions with i.v. immunoglobulin.

The aim of this trial was to investigate whether infusions of i.v. immunoglobulins (Ig) to women with secondary recurrent spontaneous abortions and recurrent second trimester spontaneous abortions can increase the rate of successful pregnancy. In a prospective, double-blind, placebo-controlled trial, infusions of i.v. Ig (Nordimmun) or placebo were given during pregnancy to 34 women with a history of either unexplained recurrent spontaneous abortion subsequent to a birth or including at least one second trimester miscarriage. The success rate was 52.9% in the i.v. Ig group compared with 29.4% in the placebo group (not significantly different, therapeutic gain 23.5%, 95% confidence interval -8.6 to 55.7%). No changes in autoantibody concentrations or major lymphocyte subsets were induced by i.v. Ig treatment. In conclusion, an expected 55% therapeutic gain of i.v. Ig in recurrent spontaneous abortion could not be confirmed using the treatment regimen tested. However, to determine whether the trend of therapeutic gain of i.v. Ig in these women may be statistically significant, a larger trial is in progress.

Abortion, Habitual↗

PubMed1995

Ethanol inhibits acetate metabolism in rat hepatocytes.

The metabolism of acetate at concentrations of 1, 2.5, 5 and 10 mM was investigated in freshly isolated hepatocytes from 48 hr fasted, female rats in the absence and presence of 10 mM ethanol. The maximal capacity for acetate metabolism was 0.85 mumol/(10(8) cells.min). Ethanol caused a 20% decrease in the apparent Vmax for acetate metabolism and an increase in the apparent Km for acetate from 3.0 to 4.6 mM. At physiological concentration of acetate (approximately 1 mM) and in the absence of an inhibitory effect of ethanol, the capacity for acetate metabolism was 15-20% of the rate of acetate formation from ethanol and the inhibitory effect of ethanol further reduced it to 10-15%. The results thus explain the well-known but hitherto not understood fact that only a small fraction of acetate produced in the liver during ethanol oxidation is further metabolized by the liver, while the majority is exported for oxidation in other tissues. Finally, a new method for calculation of liver acetate uptake in the presence of ethanol is presented.

Acetates↗

PubMed1995

Maternal HLA class II allogenotypes are markers for the predisposition to fetal losses in families of women with unexplained recurrent fetal loss.

The HLA allogenotypes DR1/Br, DR3 and DR10 (entitled risk HLA markers) have been reported as being genetic markers for the predisposition to experience unexplained recurrent fetal losses. The aim of the study was to determine whether the putative risk HLA markers might also be markers for the risk of pregnancy loss in sisters and wives of brothers of women with unexplained recurrent fetal losses. Information concerning pregnancy outcomes among the relatives of 146 consecutive women with unexplained recurrent fetal losses was collected. Ninety-five of the full sisters, 69 of the full brothers and 50 of the wives of the brothers were HLA typed. Sisters who had experienced at least one previous pregnancy loss (affected women) shared more HLA haplotypes with the proband than unaffected sisters, when the proband was positive for the risk markers (P = 0.02). More affected than unaffected sisters and brothers' wives were positive for the risk markers (P < 0.005 and P < 0.03; respectively). The lowest estimate of the odds ratio for experiencing pregnancy loss among sisters and brothers' wives who were positive compared with those negative for the risk markers was 3.5 (95% credible interval = 1.9-5.8). It is concluded that maternal DR1/Br, DR3 and DR10 allogenotypes seem to be genetic markers for the risk of pregnancy loss among relatives of women with unexplained recurrent fetal losses. The pattern of inheritance suggests a polygenic mode of inheritance with alleles linked to the risk HLA markers interacting with non-HLA linked genes expressed on the fetus or the trophoblast.

Abortion, Habitual↗

PubMed1995

Lymphocyte redistribution in connection with physical activity in the rat.

Previous studies have demonstrated numerous immunobiological changes in connection with exercise. A decrease in peripheral blood mononuclear white cells (PBMC) 2 h after intense exercise has been shown. This lymphocytopenia in humans after exercise is thought to be of great importance regarding the morbidity to viral infection. We constructed an animal experimental set-up, previously published, to investigate the exercise-induced lymphocyte redistribution. The experimental set-up allowed us to draw blood from catheters implanted in the right carotid artery in rats. PBMC were isolated and labelled with In111 and reinfused before the exercise run on a treadmill to exhaustion. The runner and control rats were killed and dissection performed 1 h after the exercise. Tissue samples were weighed and measured in a gamma counter. Furthermore, blind microscopic examinations of selected tissues were performed to study a hypothesized accumulation of blood mononuclear cells in relation to muscle fibre lesions. We found that the total number of PBMC in the running rats was decreased (P = 0.018) and granulocytes increased, 1 h after the exercise (P = 0.028). Similar findings in humans in connection with physical activity have been observed. The percentage of total injected counts per minute per gram tissue (% c.p.m. g-1) showed significantly lower values in the liver and kidney from runners than from controls (P = 0.032 and P = 0.028). These findings might be the result of a visceral hypoflow in connection with exercise. Furthermore, a tendency to decreased % c.p.m. g-1 in the lungs were seen in the exercised rats (P = 0.083) indicating a possible redistribution from the lungs during the run. Light microscopy demonstrated an accumulation of PBMC around muscle fibre lesions, but there was no significant difference between runners and controls. Furthermore, no significant difference in % c.p.m. g-1 was found between working muscle groups in runner and control rats. In conclusion, the demonstration of the redistribution of PBMC from the liver and kidney in the exercised rats and the absence of any significant accumulation of PBMC in working muscles or other organs, do not explain the lymphocytopenia demonstrated here.

Adjuvants, Immunologic↗

PubMed1995

The effect of n-3 fatty acids on neutrophil chemiluminescence.

The effect of dietary supplementation with n-3 polyunsaturated fatty acids (PUFAs) on the production of free oxygen radicals from activated neutrophils was investigated in healthy subjects, using chemiluminescence. In the first study 22 persons were give 4 g n-3 PUFAs daily for 6 weeks. There was a median reduction of chemiluminescence from neutrophils stimulated with opsonized zymosan of 37% (p < 0.001). The median content of eicosapentaenoic acid in platelets, used as an indicator for cellular fatty acid profile, increased from 0.70 to 2.80% (p < 0.001), and there was a significant negative correlation between the chemiluminescence signal and the content of eicosapentaenoic acid in platelets (p < 0.001). In a second, low-dose study 24 persons were allocated to daily supplementation with either 0.65 g n-3 PUFAs or with a control oil for 6 weeks. Compared to the control group there was a median reduction of 38 and 44% in chemiluminescence from neutrophils stimulated with opsonized zymosan and phorbol,12-myristate,13-acetate (PMA), respectively. Neither of these differences, however, was statistically significant. These findings lend support for a possible role of n-3 PUFAs in the management of inflammatory disorders.

Adult↗

PubMed1994

[Immunological techniques in unexplained thrombocytopenia. A case of specific diagnosis of post-transfusion purpura].

A case of post-transfusion purpura is presented. The diagnosis is based on two new techniques with immunological aspects: 1) Monoclonal Antibody Immobilization of Platelet Antigen assay (MAIPA-assay) and 2) Polymerase Chain Reaction assay (PCR-assay). MESH: Thrombocytopenia. Post-transfusion purpura. Monoclonal Antibody Immobilization of Platelet Antigen assay (MAIPA-assay). Polymerase Chain Reaction assay (PCR-assay).

Antibodies, Monoclonal↗

PubMed1994

Quantification of protein turnover in primary cultures of rat hepatocytes.

1. A radioactive tracer method, based on [3H]valine, for determination in parallel experiments of degradation of cellular proteins and synthesis of both cellular and secreted proteins in cultured rat hepatocytes was developed with special emphasis on methods of calculation, the number of protein pools and maintenance of nitrogen balance. 2. An extracellular concentration of 2 mM valine ensured a specific activity of the precursor pool for protein synthesis, which was constant during the experimental period and practically identical to that of extracellular valine. 3. Amino acid concentrations in the culture medium used were not rate-limiting for the synthesis of proteins. 4. The rate of labelling of the cellular protein pool during 8 days was in accordance with first-order saturation kinetics, which together with a constant ratio between labelling of soluble and membrane bound proteins, is compatible with a single pool of cellular proteins. 5. Protein degradation can be accurately measured by the release from prelabelled proteins of [3H]valine in the presence of 2 mM extracellular valine, if a 1 h chasing period is included in the experimental design. 6. The constancy of the degradation constant (kd) during protein labelling for up to 8 days, is in accordance with the existence of only one pool of cellular protein. 7. The cultured hepatocytes were in nitrogen balance during the experimental period of 8 days as reflected in a constant protein content per cell. The absolute rates of degradation and synthesis of cellular protein were identical, which confirm the validity of the method described.

Animals↗