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Biomedical subjects

M Hansson

Publications and source records attributed to M Hansson.

143 records · Page 8Linked to original sources
PubMed1980

Demonstration of natural antibodies in normal rabbit serum with similar specificity pattern as mouse natural killer cells.

Normal rabbit sera (NRS) obtained from noninbred animals were shown to contain antibody to YAC-1, a mouse lymphoma, in a complement-dependent 51Cr release assay. A positive correlation was found between the sensitivity to lysis by NRS antibody and the susceptibility to lysis by mouse natural killer (NK) cells when 7 mouse tumors and 1 guinea pig hepatoma were tested in both assay systems. This correlation was further established with a quantitative absorption assay in which NRS was absorbed with various mouse tumors and subsequently tested for cytotoxicity against YAC-1, the most NRS- and NK-sensitive tumor. A striking positive correlation appeared between the capacity to absorb the NRS anti-YAC-1 activity and the NK sensitivity of various mouse tumors to CBA spleen cells. Thymocytes from strain A/Sn mice less than 2 weeks old absorbed a substantial amount of the NRS anti-YAC-1 activity; these cells were also sensitive to mouse NK cytolysis, whereas thymocytes from older mice lacked both properties. These natural rabbit antibodies could not "arm" peripheral blood lymphocytes in the rabbit because 1) the peripheral blood lymphocytes from these animals used as serum donors showed only low cytotoxic activity in an NK assay against NK-sensitive mouse tumors, and 2) no positive correlation appeared between the levels of cytolytic activity and the levels of natural serum antibodies observed in the rabbits. The present data suggest that natural antibodies in NRS showed the same specificity pattern for mouse tumors displayed by mouse NK cells.

Age Factors↗
PubMed1980

Target-effector cell interaction in the natural killer cell system. V. Energy requirements, membrane integrity, and the possible involvement of lysosomal enzymes.

Various inhibitors were used to study further the mechanism of natural killing and to compare it to lympholysis by cytotoxic T lymphocytes (CTL). The respiratory inhibitors DNP and NaN3 or low temperatures (0 degrees) blocked the cell contact phase of target-effector interaction in the CTL system but not the NK system. The lytic stage was also inhibited by the glycolytic inhibitors, iodoacetate and NaF, in the NK system as previously shown in the CTL system. Dimethylsulphoxide, a dipolar solvent, and cytochalasin B, a microtubule disruptor, inhibited NK target binding. Pre-treatment of Nk cells with glutaraldehyde, a protein cross-linking agent, completely prevented lysis, but not the formation of target-effector conjugates. The lytic phase of NK lysis was inhibited by chloroquine which also inhibited lysosomal enzyme function. Lysosome defective, beige mutant mice were also totally deficient in NK lytic function and this defect could not be restored with cGMP. T-cell and macrophage mediated cytolysis was previously shown to be relatively normal in beige mice. These results suggest that (i) the mechanism of NK cytolysis is a complex, multistep process, and (ii) this process is fundamentally different from that occurring in CTL. A 'stimulus-secretion' model of NK cytolysis is presented in which it is postulated that lysosomal enzymes may be the lytic molecules.

Animals↗
PubMed1978

Intra- and interspecies reactivity of human and mouse natural killer (NK) cells.

Natural killer (NK) cells can kill certain syngeneic, allogeneic and xenogeneic tumor targets in short-term 51Cr release assays. In the present study, intra- and interspecies NK activity was analyzed. Ten mouse and five human tissue culture lines were used. In direct cytolytic assays with mouse spleen cells or human PBL effectors, intraspecies was much stronger than interspecies reactivity, as a rule. A certain interspecies activity was obtained, stronger in mouse anti-human (M alpha H) than in human anti-mouse (H alpha M) combinations. In the H alpha M system, activity was associated with the same type of PBL-derived non-B-non-T cell fraction as in the intraspecies H alpha H system. The non-B-non-T cell nature of the M alpha H killer cell has been demonstrated previously. Nonlabeled tumor cells were allowed to compete with isotope-labeled targets in intra- and interspecies cytolytic NK tests. NK-sensitive tumor lines of the same species were superior to xenogeneic competitors in both M alpha M and H alpha H tests. In the M alpha M assay, the competing ability of the same human tumors varied, depending on the genotype of the mouse effector cells. None of the human lines tested competed effectively with strain CBA effectors but some showed a certain competition with C57BL effectors. In the H alpha H assay, strong competition was seen with two of the 10 xenogeneic mouse tumors tested.

Animals↗
PubMedDate not supplied

Increase of serum interleukin-2 and regression of myeloma after rhGM-CSF treatment of drug induced bone marrow aplasia.

Recombinant human granulocyte/macrophage colony-stimulating factor (rhGM-CSF) was administered to a patient with multiple myeloma (IgA, stage IIA) who had a chemotherapy-induced bone marrow aplasia with granulocytopenia complicated by severe pneumonia and septicemia. The rhGM-CSF was given as i.v. infusions, 300-400 micrograms daily, for three weeks. The patient responded both hematologically and clinically with improved granulocyte counts and clearance of massive pulmonary infiltrates. We also observed a partial remission of the myeloma with decreasing s-IgA levels and reduced plasma cell infiltration of the bone marrow during a period of up to four months after the rhGM-CSF treatment. Immunological studies performed during and after cytokine administration showed an increase in serum interleukin-2 (IL-2) levels and HLA-DR positive T-lymphocytes indicating an activation of the immune system. It is suggested that rhGM-CSF induced immunological changes which may have contributed to the partial regression of the myeloma.

Aged↗
PubMedDate not supplied

Relationships between adherence, sense of coherence, and knowledge in cardiac rehabilitation.

Seventy-nine subjects took part in a cross-sectional study to investigate knowledge of and adherence to lifestyle recommendations 2 years after cardiac rehabilitation. The relationship of adherence, Antonovsky's sense of coherence (SOC) concept, and knowledge also were explored. Data were collected via a mailed questionnaire. The majority of the subjects showed a high degree of program-related knowledge and a significant increase in desired behaviors. A modest correlation was found between knowledge and SOC, whereas, contrary to expectations, there was no significant association between SOC and adherence. The results question the concept of adherence to medical regimens as a measure of successful coping.

Adaptation, Psychological↗
PubMedDate not supplied

EM single particle analysis of the ATP-dependent BchI complex of magnesium chelatase: an AAA+ hexamer.

BchI, belonging to the AAA+ -protein family, forms the enzyme magnesium chelatase together with BchD and BchH. This enzyme catalyses the insertion of Mg2+ into protoporphyrin IX upon ATP hydrolysis. Previous studies have indicated that BchI forms ATP-dependent complexes and it is a member of the AAA+ -protein family (ATPases associated with various cellular activities) and it was suggested based on structural homology that the BchI formed hexameric complexes. AAA+ -proteins are Mg2+ -dependent ATPases that normally form oligomeric ring complexes in the presence of ATP. Single particle analysis of fully formed ring complexes of BchI observed by negative staining EM indicate that the BchI has strong 6- and 2-fold rotational symmetries and a weaker 4-fold rotational symmetry which are reminiscent of DNA helicase. A 2D average of the fully formed BchI-ATP ring complex is presented here from images of the complex obtained from negative staining EM. Other complexes are also observed in the EM micrographs and the class averages of these are indicative of the fragility and dynamic nature of the BchI complex which has been reported and they are suggestive of partially circular complexes with six or less protomers per particle. The resolution of the average circular complex is estimated at approximately 30A and it is similar in shape and size to an atomic resolution hexameric model of BchI rendered at 30A.

Adenosine Triphosphatases↗
PubMedDate not supplied

Genetic control of resistance to mercury-induced immune/autoimmune activation.

Previous studies have shown that genetic factors control the susceptibility to mercury-induced immunoglobulin (Ig)G1 antibody formation, IgE synthesis, renal IgG deposits and antinucleolar autoantibodies (ANolA) production in the susceptible mice. In this study, we examined the genetic control of resistance to these characteristics after HgCl2 injection in F1 hybrid crosses between the highly mercury resistant DBA/2 and mercury susceptible NZB (H-2d), SJL (H-2 s), A.CA (H-2f) and DBA/1 (H-2q) mice and also in backcross hybrids between (DBA/2 x SJL)F1 and SJL mice. We observed that mercury-induced immune/autoimmune manifestations were profoundly downregulated in most (if not all) of the F1 hybrids, indicating that the resistance to mercury was a dominant trait. Analysis of mercury-induced immune/autoimmune responses in the (DBA/2 x SJL) x SJL backcross hybrids suggested that only one gene or a cluster of genes determined the resistance to the ANolA production, whereas the resistance to other characteristics was controlled by two and/or three gene loci. By H-2 genotyping the backcross mice, it was found that H-2d haplotype per se could confer resistance to ANolA production. However, we did not find any significant association between the H-2d haplotype and the resistance to increase of IgG1 and IgE synthesis and the development of renal IgG1 deposits. Thus, while in DBA/2 mice, gene(s) in the H-2 loci strictly contribute to the inheritance of resistance to ANolA production; non-H-2 genes mainly govern the inheritance of unresponsiveness regarding other characteristics.

Animals↗
PubMedDate not supplied

Non-lytic pre-NK cells are enriched in the spleen as a result of long-term depletion of mature NK cells with anti-NK-1.1 monoclonal antibody.

In this study, we wanted to establish a new model as an alternative to bone marrow, where non-lytic pre-NK cells can be further studied with respect to phenotype and relation to other haematopoietic cell lineages. B6 mice were depleted of mature NK cells by either weekly injections from birth, or a single injection as adults, with the monoclonal antibody anti NK-1.1, and the frequency of interleukin-2 (IL-2)-responding cells (as determined by cytotoxicity or proliferation) was investigated. By comparing the frequency of IL-2-induced cytotoxic cells between NK-1.1(-) mice depleted from NK cells by a single injection with those depleted from birth, we observed a 3-fold higher frequency in mice depleted from birth [1/(11,941 +/- 30) vs. 1/(29,903 +/- 104)]. Non-lytic pre-NK cells were further enriched by selective in vitro depletion of sIg+, CD4+ and CD8+ cells. In this non-B, non-T spleen cell population the frequency of cells proliferating in response to 7 days culture with IL-2 or IL-3 was 2-fold higher in NK-1.1(-) mice than in control mice [1/(4,340 +/- 27) vs. 1/(9,250 +/- 67) and 1/(3,370 +/- 41) vs. 1/(7,610 +/- 50), respectively]. We conclude that NK depletion from birth results in an enhanced frequency of pre-NK cells, and propose this as a model to further study the identity of the progenitor and pre-NK cell.

Animals↗
PubMedDate not supplied

Tumor necrosis factor-alpha and interferon-gamma in serum of multiple myeloma patients.

The levels of TNF-alpha and IFN-gamma were examined in serum from 32 patients with multiple myeloma and 33 healthy controls using sensitive enzyme-linked immunosorbent assays (ELISA). The detection limits for TNF-alpha and IFN-gamma were 80 pg/ml and 200 pg/ml, respectively. All samples were obtained at the time of diagnosis, before treatment. In sera from 8 of the myeloma patients the TNF-alpha concentrations were above the detection limit with a maximum value of 1.0 ng/ml. Overall, the TNF-alpha levels of the myeloma patients did not differ from the levels of the control group. Detectable amounts of IFN-gamma were found in 17 of the patient sera with 10.7 ng/ml as the top value. In contrast, the control group showed significantly lower s-IFN-gamma levels without detectable amounts in any of the samples (p less than 0.01). High IFN-alpha levels in 4 patients coincided with intercurrent infections but were not accompanied by a parallel increase of the TNF-alpha levels. The TNF-alpha and IFN-gamma values were compared with the serum levels of beta 2-microglobulin, calcium and creatinine, the M-component, the erythrocyte sedimentation rate, the degree of plasma cell infiltration of the bone marrow, the degree of skeletal destructions and with patients survival. No significant correlations could be observed between TNF-alpha or IFN-gamma and these variables of myeloma activity. We conclude that detection of serum TNF-alpha and IFN-gamma levels in multiple myeloma appears to be without any clinical value.

Aged↗
PubMedDate not supplied

Inhibition of mouse bone marrow granulocyte-macrophage colony formation by factors derived from natural killer cells: an in vitro model for hybrid resistance.

Investigations were performed to study whether soluble factors produced by NK-cells could mediate "hybrid resistance" in vitro. NK-cells enriched from spleens of B6D2F1 hybrid mice were incubated with parental B6 bone marrow, and the effect of the derived supernatants on the development of granulocyte-macrophage colony forming cells (GM-CFC) was assessed. Cell free supernatants obtained from low density cells (LDC) of B6D2F1 hybrids stimulated with bone marrow cells (BMC) from B6 mice inhibited GM-CFC formation. The inhibition was similar using B6, D2 or B6D2F1 bone marrow cells as the targets for GM-CFC growth. Our findings suggest that NK cells from F1 hybrid mice when stimulated with BMC from B6 mice release inhibitory factors, different from IFN-gamma and that this production may represent a mechanism of natural resistance to parental H-2b bone marrow grafts.

Animals↗
PubMedDate not supplied

IFN-gamma is not the only mediator of suppressed myelopoiesis produced by mononuclear cells from aplastic anemia patients.

Peripheral blood mononuclear cells (PBMC) from patients with aplastic anemia (AA) and healthy donors were compared with regard to their ability to produce soluble factors with inhibitory activity on in vitro granulopoiesis (GM-CFC). Although PBMC from AA patients produced enhanced levels of IFN-gamma as compared to controls, this lymphokine was found not to be the main inhibitor of in vitro granulopoiesis. Other, non-IFN related factors were potent inhibitors of both the mature and the immature precursors for GM-CFC, could act across the species barrier and were of low molecular weight. Also PBMC from healthy donors produced a non-IFN mediated GM-CFC inhibitory factor, but to a lesser degree and acting only on one type of myeloid precursors. The possible implications of these findings in relation to the etiology of AA will be discussed.

Adult↗