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A Husebekk

Publications and source records attributed to A Husebekk.

At least 19 recordsLinked to original sources
PubMed2005

Increased frequency of antral CD4 T and CD19 B cells in patients with Helicobacter pylori-related peptic ulcer disease.

Only a fraction of Helicobacter pylori (HP)-infected individuals develop clinical disease. Recent research indicates that immunological mechanisms may be important for understanding the pathophysiology of HP infection. Differences in the individual cellular immune response may reflect the clinical diversity. The aim of the present study was to investigate the cellular immune response against HP in three clinically well-defined patient groups: HP-positive peptic ulcer, HP-positive and HP-negative gastritis. Biopsies from gastric mucosa were processed for analysis by flow cytometry and histology. The number of T lymphocytes (CD3+) was significantly higher in HP-positive peptic ulcer (13.8%) than in HP-positive nonulcer gastritis (6.3%). A nonsignificant increase for B lymphocytes (CD19+) was noted as well. Furthermore, a significant difference was seen in mucosal CD4/CD8 ratio between HP ulcer (2.4) and nonulcer HP gastritis (1.0) patients. Thus, B cells (CD19+) and T-helper cells (CD4+) were dominant in gastric mucosa from peptic ulcer patients, and cytotoxic T cells (CD8+) were relatively dominant in gastric mucosa from nonulcer patients. In conclusion, distinct differences in the T-cell subset distribution of mucosal lymphocytes were detected in patients with HP infection, strongly correlated with the presence or absence of peptic ulcer.

Adult↗
PubMed2001

[Significance of maternal alloantibodies for neonatal thrombocytopenia].

BACKGROUND: Thrombocytopenia has been shown to be present in about 1% of unselected newborns. Alloantibodies to platelets induce the most severe thrombocytopenia. MATERIAL AND METHODS: Samples from 195 mothers who had just given birth to thrombocytopenic children, were analysed by platelet antigen genotyping and detection of platelet specific antibodies. RESULTS: 75 mothers were typed human platelet antigen (HPA) 1bb, and in 65 mother, anti-HPA 1a antibodies could be detected. Anti-HPA 5b antibodies were detected in three samples and anti-HLA antibodies in 73 samples. INTERPRETATION: Alloantibodies were shown to be an important cause of thrombocytopenia in the new-born children and anti-HPA 1a antibodies were, as expected, the most common platelet-specific antibody involved. Anti-HLA class 1 antibodies were detected as the only antibody in 51 cases of thrombocytopenia. Though it is not yet formally shown, this may indicate that anti-HLA class 1 antibodies may cause thrombocytopenia in the fetus and new-born. Based on the assumption that neonatal alloimmune thrombocytopenia is present in 1:1,000 new-born, 25% of the neonatal alloimmune thrombocytopenia cases in Norway are verified by laboratory analysis. Alloantibodies to thrombocytes are of clinical importance in future pregnancies and transfusions. The cost and benefit of a national screening program for anti-HPA 1a antibodies in all pregnant women should be carefully considered.

Antigens, Human Platelet↗
PubMed2001

Radioimmunotherapy with iodine-131 tositumomab in patients with low-grade non-Hodgkin's B-cell lymphoma does not induce loss of acquired humoral immunity against common antigens.

Thirty-one previously untreated patients with follicular low-grade B-cell non-Hodgkin's lymphoma expressing the CD20 antigen were treated with iodine-131 tositumomab therapy between 1996 and 1998. The therapy led to a temporary depletion of peripheral blood B-lymphocytes. Recovery of B-cells occurred in most cases by 3 to 6 months and in all patients by 12 months posttherapy. A temporary decline in T-cell subpopulations, but no reduction in serum immunoglobulin levels, could be observed. ELISA techniques were used to detect specific antibodies against rubella, mumps, varicella zoster, measles, and tetanus. Almost all patients remained seropositive against the different antigens during the 1- to 2-year follow-up. No significant reduction in antibody concentrations to tetanus or measles could be detected. The data show that acquired humoral immunity against common antigens appears to be preserved despite a temporary loss of B-lymphocytes.

Adult↗
PubMed2001

Humoral immunity to viral and bacterial antigens in lymphoma patients 4-10 years after high-dose therapy with ABMT. Serological responses to revaccinations according to EBMT guidelines.

The aim of this study was to investigate the late effects of ABMT on the immune system with regard to protective humoral immunity against common antigens and responses to recall antigens (vaccines). The vaccines were given according to EBMT guidelines from 1995. The protocol included 35 patients with malignant lymphoma in CR 4-10 years after ABMT, and 35 controls. The results show that prior to ABMT the proportion of patients with protective immunity against poliomyelitis, tetanus and diphtheria was similar to that of controls. At study entry 4-10 years after ABMT, the proportion of patients with protective immunity against poliomyelitis and diphtheria was reduced, while all patients maintained protection against tetanus. A significant decrease in geometric mean antibody concentrations or titres was observed against all three antigens during this period. Serum levels of antibodies against different pneumococcal serotypes were lower in the patients than in the controls prior to vaccination. The responses to pneumococcal vaccination, which is considered to be a T cell-independent vaccine, were studied. Unlike controls, a minority of patients achieved protective levels of antibodies after a single vaccination. Despite persistent levels of protective antibodies in many patients post ABMT, secondary booster responses after one vaccination with T cell-dependent vaccines (tetanus, diphtheria and polio) were absent. In conclusion, this study shows that post ABMT, a full re-vaccination program was necessary to mount responses comparable to those observed after a single vaccination in controls.

Adolescent↗
PubMed2000

Selection and expansion of T cell from untreated patients with CLL: source of cells for immune reconstitution?

BACKGROUND: Lymphocyte-derived malignancies can be treated with combinations of drugs that efficiently eradicate normal and malignant lymphocytes. Lack of T lymphocytes after treatment of B lymphocyte CLL (B-CLL) makes the patients susceptible to serious infections and may limit the benefit of the therapy. The aim of the study was to purify and culture-expand normal T lymphocytes from B-CLL patients prior to therapy. These cells could be frozen and given to the patients in the lymphopenic period post-chemotherapy. METHODS: T lymphocytes were isolated from the mononuclear cell apheresis products from five patients with previously untreated B-CLL. The apheresis products were red-cell depleted by density gradient centrifugation. B-lymphocyte purging was performed by incubating with MAbs to four different B-cell epitopes, followed by magnetic-bead depletion. One round of negative selection removed >90% of the B lymphocytes. The T-lymphocyte enriched cell suspension was cultured for 10/11 days in the presence of IL-2 and the anti-T cell receptor Ab OKT3. In addition, in some cultures anti-CD22 ricin immunotoxin was added. RESULTS: T cells from CLL patients expanded 4.7-21-fold over a 10/11 days culture interval. After culture, CLL cells could no longer be identified by flow cytometric evaluation. The cultured T lymphocytes were predominantly CD8(+), and were capable of lysing autologous CLL cells through a fas-dependent mechanism. DISCUSSION: Selection and expansion of T lymphocytes by this method may represent a strategy for enhancing immunity in the lymphopenic period following CLL treatment.

CD8-Positive T-Lymphocytes↗
PubMed2000

Neonatal alloimmune thrombocytopenia due to anti-HPA 1a antibodies; the level of maternal antibodies predicts the severity of thrombocytopenia in the newborn.

Eleven thousand one hundred pregnant women were genotyped for human platelet antigen HPA 1, and 198 HPA 1bb women were followed in the pregnancy with quantitative assay for anti-HPA la antibodies. Antibodies were detected in 24 women, and nine children were born with severe thrombocytopenia (< 50x10(9)/L). All mothers with high levels of antibodies were delivered of children with severe thrombocytopenia. None of the newborn infants had clinical signs of intra-cranial haemorrhage. The level of maternal anti-HPA 1a antibodies is predictive for fetal thrombocytopenia and may be used in decisions related to time and mode of delivery.

Antibodies↗
PubMed1999

Persistent changes in the immune system 4-10 years after ABMT.

The aim of the present study was to investigate whether the early changes in the immune system observed after ABMT would persist over years. Eighty-five patients with malignant lymphoma were treated with ABMT in Norway from 1987 until 1993. Of the 46 patients in CR by 1997, 36 were enrolled in our study. Median time from ABMT was 5 years (4-10 years). Immunophenotyping showed an increase in the median number of B cells (0.35 x 109/l in patients vs 0.28 x 109/l in controls), and a decrease in T cells (1.08 vs 1.35 x 109/l). Furthermore, a lower median count of CD4+ T cells (0.54 x 109/l in patients vs0.87 x 109/l in controls) resulted in reduced CD4/CD8 ratios (0.8 in patients vs 1.6 in controls). The subgroup of CD4+ T cells expressing the 'naive' phenotype CD45RA was 19.5% in patients vs 38% in controls. In contrast, the fraction expressing the 'memory' phenotype CD45RO was higher in the ABMT group (76% vs 54%). When stimulated, larger fractions of CD3+CD4+ cells in patients produced IFN-gamma (32% vs 16%) or IL-4 (7% vs 1%) compared to controls; thus a differentiation into the functionally separate subgroups Th1 and Th2, with a dominant Th2 response. Our data further suggest that the decrease in CD4+ T cell counts and the imbalance between CD45RA+ and CD45RO+ subsets persists 4-10 years after ABMT.

Adolescent↗
PubMed1999

fas-mediated lysis of chronic lymphocytic leukaemia cells: role of type I versus type II cytokines and autologous fasL-expressing T cells.

Given the known role of the fas cytolytic pathway in B-cell regulation, we evaluated whether fas-fasL interactions might induce chronic lymphocytic leukaemia (CLL) cell death. De novo CLL cells expressed a low level of surface fas, and were not lysed by fasL-bearing cells. CLL cells cultured in media containing the type I cytokines interleukin (IL)-12 or interferon (IFN)-alpha had increased fas expression, and were readily lysed by fasL-bearing cells. In contrast, the type II cytokine IL-4 did not increase CLL cell fas, and abrogated type I cytokine-induced fas up-regulation. With prolonged culture, IL-4 exposed CLL cells expressed an intermediate level of fas; however, such CLL cells were resistant to fas-mediated lysis. These results indicate that IL-4 inhibits fas-mediated killing of CLL cells at the level of both fas receptor expression and post-receptor events. Additionally, we have defined in vitro culture conditions which generate fasL-bearing T cells from CLL patients; such T cells efficiently mediated fas-based lysis of autologous fas-positive CLL cells. We therefore conclude that type I and type II cytokines differentially regulate the fas pathway in CLL cells, and that a combination of type I cytokines and fasL-expressing T cells may represent a new approach to the immunotherapy of CLL.

Apoptosis↗
PubMed1998

[Decentralized high-dose cytostatic treatment with autologous stem cell support].

In the past high-dose chemotherapy with autologous stem cell support in the treatment of certain types of cancer, was centralized to two hospitals in Norway. Almost three years ago it was decided that the treatment should be offered by all five university hospitals. In the northernmost university hospital of Norway, Tromsø, peripheral stem cells were harvested from 29 patients after successful mobilization with chemotherapy and granulocyte colony-stimulating factor (G-CSF). After high-dose chemotherapy, more than 2 x 10(6) CD34-positive stem cells/kg were transplanted in 24 patients and a sign of reconstitution of bone marrow function was achieved with mean time for neutrophils > 0.5x10(9)/l, 9.8 days and for platelets > 20x10(9)/l, 10.8 days. No treatment-related deaths have occurred. Transplantation of selected CD34-positive stem cells has been performed in one patient. Recovery was comparable to the recovery of patients who had undergone transplantation with unselected products. This indicates that even small centres performing as few as ten procedures per year may offer high-dose chemotherapy with autologous stem cell support safely and successfully.

Antigens, CD34↗
PubMed1998

Improved method for serological testing in celiac disease--IgA anti-endomysium antibody test: a comparison between monkey oesophagus and human umbilical cord as substrate in indirect immunofluorescence test.

The IgA anti-endomysium antibody (IgA-EmA) test has been studied using the indirect immunofluorescence (IF) method with human umbilical cord (HUC) as substrate; 247 sera from patients investigated for celiac disease were tested. The results were in accordance with those obtained using monkey oesophagus (MOE) as substrate. IgA-EmA testing using HUC is shown to have similar reproducibility, sensitivity and specificity as MOE. By avoiding both fixation in chloroform and the blocking step, the processing time for this improved method is decreased by almost 1 h, and the results are stable for reading by fluorescence microscopy for at least 24 h. The indirect IF method using HUC as substrate is easy, reliable and inexpensive. We conclude that the IgA-EmA test using HUC as a substrate can be routinely used for celiac disease screening and follow up.

ABO Blood-Group System↗
PubMed1996

[Neonatal alloimmune thrombocytopenia. Diagnosis and follow-up in pregnancy].

Neonatal alloimmune thrombocytopenia is present in every 2,000-3,000 pregnancy, that is in 20-30 pregnancies in Norway each year. Anti-HPA la antibodies are usually present in severe alloimmune thrombocytopenia in foetus and neonates. Pregnant women are not screened for the presence of anti-HPA la antibodies. Neonatal alloimmune thrombocytopenia can be suspected in newborn children who show signs or symptoms of thrombocytopenia. Laboratory investigation for neonatal alloimmune thrombocytopenia should be performed if the newborn child shows signs of bleeding, in women who have had multiple abortions and after stillbirth. Examples are presented from laboratory investigations in seven families with children who have thrombocytopenia.

Blood Platelets↗
PubMed1996

Experimental AA-amyloidosis in mice is inhibited by treatment with the anti-rheumatic drug tenidap.

In a mouse model for induction of experimental AA-amyloidosis, treatment with tenidap was shown to inhibit the development of amyloidosis. Studies have shown that the drug inhibits the cytokines interleukin (IL)-6, IL-1 and tumour necrosis factor alpha (TNF-alpha) which are known to stimulate hepatocytes to synthesize acute phase proteins (APPs). The APP serum amyloid protein (SAA) is the precursor for amyloid protein AA and tenidap treatment reduces the serum levels of SAA in mouse and humans. It is suggested that reduction of SAA levels reduces the risk of AA fibril formation and thus the development of amyloidosis.

Amyloidosis↗
PubMed1995

Flow cytometric analysis in platelet crossmatching using a platelet suspension immunofluorescence test.

BACKGROUND: The sensitivity of flow cytometric measurement of platelet antibodies in a crossmatch technique was investigated. STUDY DESIGN AND METHODS: The corrected count increment after platelet transfusion was compared with the fluorescence ratio determined by flow cytometric measurement. RESULTS: When crossmatching was performed before transfusion(s) in alloimmunized patients, a fluorescence ratio < or = 1.7 was associated with satisfactory responses (corrected count increment > or = 7.5), and the predictive values for negative and positive crossmatch results were 94 and 87 percent, respectively. Analysis of antigen preservation during platelet storage with antibodies to HLA alpha-chain, HLA-B27, HPA-1a, and HPA-3a showed that platelets can be stored, refrigerated, for up to 4 weeks without significant loss of HLA class I and HPA-1a. There was a slight but continuous loss of HPA-3a upon storage. CONCLUSION: Flow cytometric measurement of fluorescence in the platelet suspension immunofluorescence test can be used for platelet crossmatching, with sensitivity and predictive values comparable to those of previously described techniques and with the advantage of automation.

Antigens, Human Platelet↗
PubMed1994

Cells of Th2 cytokine phenotype prevent LPS-induced lethality during murine graft-versus-host reaction. Regulation of cytokines and CD8+ lymphoid engraftment.

A murine parent-into-F1 graft-vs-host reaction (GVHR) model that utilizes LPS to induce lethality was used to evaluate the in vivo regulatory role of donor cells of Th2 cytokine phenotype. Transfer of B6 spleen cells into B6C3F1 hosts was lethal when LPS endotoxin (15 micrograms) was administered on day 7 after cell transfer. Parental cells of Th2 cytokine phenotype were generated by treating B6 mice in vivo with a combination of IL-2 and IL-4 or with high dose IL-2. The CD4-enriched population from these cytokine-treated mice expressed and secreted increased levels of IL-4 and IL-10, with concomitantly decreased IL-2 and IFN-gamma. Cell mixing experiments (parental spleen cells+parental CD4-enriched. Th2-type cells) demonstrated that the Th2-type cells protected F1 hosts from LPS-induced lethality. These mice were analyzed to study possible mechanisms by which this protection was mediated. Compared with mice undergoing LPS-induced lethality during GVHR, Th2-protected mice had: 1) lower levels of donor CD8+ lymphoid engraftment, 2) in vivo suppression of IFN-gamma mRNA, 3) in vivo augmentation of IL-4 mRNA, and 4) a reduction in serum TNF-alpha. We thus conclude that donor cells of Th2 cytokine phenotype prevent LPS-induced, TNF-alpha-mediated lethality during GVHR, and that this protection is associated with regulation of both cellular- and cytokine-mediated events. As a result, we propose that cells of Th2 cytokine phenotype may represent a novel approach for establishing allogeneic lymphoid engraftment without lethal graft-vs-host disease.

Animals↗