| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Ohlin, M., et al.
(författare)
-
Epstein-Barr virus-induced transformation of human B lymphocytes : the effect of l-leucyl-l-leucine methyl ester on inhibitory T cell populations
- 1992
-
Ingår i: Immunology Letters. - 0165-2478. ; 34:3, s. 221-228
-
Tidskriftsartikel (refereegranskat)abstract
- Epstein-Barr virus-mediated transformation of human B lymphocytes is inhibited by human T lymphocytes as well as by interferon-γ. Removal of the inhibitory cell populations is essential in order to achieve successful transformation in vitro. Cells with the capacity to inhibit outgrowth of lymphoblastoid cell lines can be removed by pretreatment of peripheral blood mononuclear cells with l-leucyl-l-leucine methyl ester. This treatment eliminates monocytes, NK-cells and a CD8+ T cell subpopulation. We now show that such treatment also has toxic effects on other human T cell populations. In addition, CD4+ and/or CD8+ lymphocytes are demonstrated to contain effector cell activities which inhibit outgrowth of EBV-transformed B cells. This inhibitory activity is abolished after treatment of peripheral blood mononuclear cells or purified CD4+ T cells with l-leucyl-l-leucine methyl ester. No evidence was found for a selective toxicity against any subset within the CD4+ or CD8+ T cell populations. However, the capacity of the treated cells, both peripheral blood mononuclear cells and purified CD4+ T lymphocytes, to produce mRNA encoding IFN-γ, a protein previously shown to downregulate outgrowth of EBV-transformed B cells, was selectively impaired. The results obtained suggest a role for CD4+ T cells to inhibit EBV-induced transformation of B cells.
|
|
| 6. |
- Schoppel, K., et al.
(författare)
-
Antibodies specific for the antigenic domain 1 of glycoprotein B (gpUL55) of human cytomegalovirus bind to different substructures
- 1996
-
Ingår i: Virology. - : Elsevier BV. - 0042-6822. ; 216:1, s. 133-145
-
Tidskriftsartikel (refereegranskat)abstract
- Glycoprotein B (gB, gpUL55) is a major antigen for the induction of neutralizing antibodies against human cytomegalovirus, making it an attractive antigen for active and passive immunoprophylaxis. The immunodominant region on gB is the antigenic domain 1 (AD-1), a complex structure which requires a minimal linear amino acid sequence of more than 75 amino acids (aa 552-635) for antibody binding. We have analyzed the fine specificity cf neutralizing and nonneutralizing AD-1-binding monoclonal antibodies. Point mutations were introduced into AD-1 and mutants were expressed as bacterial fusion proteins. The antigens were analyzed in immunoblots using a panel of 13 human and murine monoclonal antibodies. Complete loss of binding of all antibodies was observed with mutations at cysteine residues 573 and 610 as well as with a combinatorial exchange of prolines at position 577 and 613. The remaining mutations had different effects on antibody binding. Six individual recognition patterns were observed, indicating various antigenic substructures on AD-1. Changing the Fc portions of 3 murine monoclonal antibodies to human IgG1 showed that neutralization of AD-1-binding immunoglobulins is exerted by different mechanisms. Dependent on the recognized substructure within AD-1, avidity-dependent as well as Fc portion-mediated effects were observed.
|
|
| 7. |
|
|
| 8. |
- Abul-Kasim, Kasim, et al.
(författare)
-
Measurement of vertebral rotation in adolescent idiopathic scoliosis with low-dose CT in prone position - method description and reliability analysis
- 2010
-
Ingår i: Scoliosis. - : Springer Science and Business Media LLC. - 1748-7161. ; 5, s. 1-8
-
Tidskriftsartikel (refereegranskat)abstract
- Background: To our knowledge there is no report in the literature on measurements of vertebral rotation with low-dose computed tomography (CT) in prone position.Aims: To describe and test the reliability of this new method, compare it with other methods in use and evaluate the influence of body position on the degree of vertebral rotation measured by different radiological methods.Study design: Retrospective study.Methods: 25 consecutive patients with adolescent idiopathic scoliosis scheduled for surgery (17 girls, 8 boys) aged 15 ± 2 years (mean ± SD) were included in the analysis of this study. The degree of the vertebral rotation was in all patients measured according to the method of Perdriolle on standing plain radiographs and on supine CT scanogram, and according to the method of Aaro and Dahlborn on axial CT images in prone position and on magnetic resonance imaging (MRI) in supine position. The measurements were done by one neuroradiologist at two different occasions. Bland and Altman statistical approach was used in the reliability assessment.Results: The reliability of measuring vertebral rotation by axial CT images in prone position was almost perfect with an intraclass correlation coefficient of 0.95, a random error of the intraobserver differences of 2.3°, a repeatability coefficient of 3.2° and a coefficient of variation of 18.4%. Corresponding values for measurements on CT scanogram were 0.83, 5.1°, 7.2°, and 32.8%, respectively, indicating lower reliability of the latter modality and method. The degree of vertebral rotation measured on standing plain radiographs, prone CT scanogram, axial images on CT in prone position and on MRI in supine position were 25.7 ± 9.8°, 21.9 ± 8.3°, 17.4 ± 7.1°, and 16.1 ± 6.5°, respectively. The vertebral rotation measured on axial CT images in prone position was in average 7.5% larger than that measured on axial MRI in supine position.Conclusions: This study has shown that measurements of vertebral rotation in prone position were more reliable on axial CT images than on CT scanogram. The measurement of vertebral rotation on CT (corrected to the pelvic tilt) in prone position imposes lower impact of the recumbent position on the vertebral rotation than did MRI in supine position. However, the magnitude of differences is of doubtful clinical significance.
|
|
| 9. |
|
|
| 10. |
- Andersson, Eva, et al.
(författare)
-
CD4+CD57+ T cells derived from peripheral blood do not support immunoglobulin production by B cells
- 1995
-
Ingår i: Cellular Immunology. - : Elsevier BV. - 0008-8749. ; 163:2, s. 245-253
-
Tidskriftsartikel (refereegranskat)abstract
- A small subpopulation of CD4+ T cells found in peripheral blood coexpresses the CD57+ marker normally found on, e.g., NK cells. It is known that this population occurs in a higher frequency in certain diseases. The same antigen has also been shown to be expressed on CD4+ T cells derived from germinal centers. The localization of this cell population to specialized lymphoid structures suggests that it may play a role in the evolution of the antibody response following antigenic stimulation in vivo. We have examined the ability of peripheral blood helper T cells coexpressing CD57 to participate in B cell activation/differentiation and evaluated their responses to polyclonal stimulation. The CD4+CD57+ T cells do not express mRNA for a number of different cytokines or for the CD40 ligand after activation in vitro. Furthermore these cells do not induce differentiation of B cells into immunoglobulin-producing cells. Consequently, despite their CD4 phenotype and their ability to be activated, to express the IL-2 receptor, and to enter into the cell cycle, they do not act as T helper cells under conditions where CD4+/CD57- cells normally do so. The findings suggest that this peripheral blood helper T cell population is functionally different from regular CD4+ T cells. The basis for the lack of proper costimulatory signals for immunoglobulin production might be related to the low expression of CD28.
|
|
| 11. |
- Andersson, Eva, et al.
(författare)
-
Immunoglobulin production induced by CD57+ GC-derived helper T cells in vitro requires addition of exogenous IL-2
- 1996
-
Ingår i: Cellular Immunology. - : Elsevier BV. - 0008-8749. ; 169:2, s. 166-173
-
Tidskriftsartikel (refereegranskat)abstract
- Germinal centers (GC) are well-defined areas in lymphoid organs were B cells proliferate and differentiate in response to T-cell-dependent antigens. The GC comprises B cells, follicular dendritic cells, tangible body macrophages, and a low number of CD4+ T cells. A large portion of these T cells expresses CD57. We have examined the ability of the CD4+CD57+ GC T cells to become activated and to take part in B cell activation processes, These T cells coexpress CD45RO, CD69, CD28, and upon mitogenic stimulation CD25, The cell population was found neither to containe nor to be able to produce any specific mRNA for IL-2, IL-4, and IFN-γ upon activation. Levels of mRNA encoding CD40 ligand was also undetectable under similar conditions. Furthermore, in contrast to ordinary CD4+ T cells, this population expressing CD57 was unable to induce B cells to Ig production in the presence of pokeweed mitogen or SEA unless IL-2 was added to the cultures, However, despite their apparent lack of function CD4+CD57+ GC T cells were found to rescue GC B cells from cell death in vitro to the same extent as CD4+CD57- T(h) cells, The phenotypical and functional differences found between these T cells and regular T(h)-cells suggest that they either represent a T cell subset with distinct properties within the GC yet to be determined or that they represent T cells, Irate in the immune response, having lost most of their original functions and capabilities.
|
|
| 12. |
- Andersson, Martin K, et al.
(författare)
-
Effects on osteoclast and osteoblast activities in cultured mouse calvarial bones by synovial fluids from patients with a loose joint prosthesis and from osteoarthritis patients.
- 2007
-
Ingår i: Arthritis research & therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 9:1
-
Tidskriftsartikel (refereegranskat)abstract
- Aseptic loosening of a joint prosthesis is associated with remodelling of bone tissue in the vicinity of the prosthesis. In the present study, we investigated the effects of synovial fluid (SF) from patients with a loose prosthetic component and periprosthetic osteolysis on osteoclast and osteoblast activities in vitro and made comparisons with the effects of SF from patients with osteoarthritis (OA). Bone resorption was assessed by the release of calcium 45 (45Ca) from cultured calvariae. The mRNA expression in calvarial bones of molecules known to be involved in osteoclast and osteoblast differentiation was assessed using semi-quantitative reverse transcription-polymerase chain reaction (PCR) and real-time PCR. SFs from patients with a loose joint prosthesis and patients with OA, but not SFs from healthy subjects, significantly enhanced 45Ca release, effects associated with increased mRNA expression of calcitonin receptor and tartrate-resistant acid phosphatase. The mRNA expression of receptor activator of nuclear factor-kappa-B ligand (rankl) and osteoprotegerin (opg) was enhanced by SFs from both patient categories. The mRNA expressions of nfat2 (nuclear factor of activated T cells 2) and oscar (osteoclast-associated receptor) were enhanced only by SFs from patients with OA, whereas the mRNA expressions of dap12 (DNAX-activating protein 12) and fcrgamma (Fc receptor common gamma subunit) were not affected by either of the two SF types. Bone resorption induced by SFs was inhibited by addition of OPG. Antibodies neutralising interleukin (IL)-1alpha, IL-1beta, soluble IL-6 receptor, IL-17, or tumour necrosis factor-alpha, when added to individual SFs, only occasionally decreased the bone-resorbing activity. The mRNA expression of alkaline phosphatase and osteocalcin was increased by SFs from patients with OA, whereas only osteocalcin mRNA was increased by SFs from patients with a loose prosthesis. Our findings demonstrate the presence of a factor (or factors) stimulating both osteoclast and osteoblast activities in SFs from patients with a loose joint prosthesis and periprosthetic osteolysis as well as in SFs from patients with OA. SF-induced bone resorption was dependent on activation of the RANKL/RANK/OPG pathway. The bone-resorbing activity could not be attributed solely to any of the known pro-inflammatory cytokines, well known to stimulate bone resorption, or to RANKL or prostaglandin E2 in SFs. The data indicate that SFs from patients with a loose prosthesis or with OA stimulate bone resorption and that SFs from patients with OA are more prone to enhance bone formation.
|
|
| 13. |
- Beding-Barnekow, B., et al.
(författare)
-
Systemic and intraocular uptake of spantide, a tachykinin antagonist, following topical application to the rabbit eye.
- 1990
-
Ingår i: Experimental Eye Research. - 0014-4835. ; 50:1, s. 21-26
-
Tidskriftsartikel (refereegranskat)abstract
- Previous observations have indicated that topical application to the rabbit eye of tachykinin antagonists, including spantide, effectively prevents the miosis and the disruption of the blood-aqueous barrier consequent to ocular injury. The present study shows that spantide is taken up into the rabbit eye following topical application. This was established by determination of spantide in the aqueous humor by radioimmunoassay. The concentrations reached in the aqueous humor were those that could be expected to block tachykinin receptors. The elimination of spantide from the aqueous humor was found to be slow. From HPLC analysis it seemed that spantide in the aqueous humor is degraded to smaller products, predominantly spantide 5–11. Some of the topically applied peptide appeared in the general circulation. Here the rate of elimination was rapid by comparison. Very small amounts of spantide appeared in the cerebrospinal fluid after intravenous injection.
|
|
| 14. |
- Bold, S., et al.
(författare)
-
Structural domains involved in human cytomegalovirus glycoprotein B-mediated cell-cell fusion
- 1996
-
Ingår i: Journal of General Virology. - 0022-1317. ; 77:9, s. 2297-2302
-
Tidskriftsartikel (refereegranskat)abstract
- A novel fusion assay was established to determine fusion activity with cocultivated human foreskin fibroblasts of stable transfectants derived from human astrocytoma cells (U373) expressing authentic or mutagenized human cytomegalovirus glycoprotein B (HCMV gB; gpUL55). Compared to transfectants expressing authentic HCMV gB, those expressing gB forms with a deletion of hydrophobic domain 1 (hd1; aa 714-747) or with deletions of specific segments in the cytoplasmic tail (aa 811-825 and 871-906) exhibited significantly reduced heterologous fusogenicity. HCMV gB-specific monoclonal antibodies (MAbs) as well as MAb against cellular annexin II prevented fusion of the transfectant expressing authentic gB. Comparable surface exposure of HCMV gB or its derivatives was demonstrated in all transfectants by FAGS analysis. Our observations are compatible with the notion that indigenous fusion activity of HCMV gB depends on the extracellular hd1 domain and on the conformation of the cytoplasmic tail.
|
|
| 15. |
- Borrebaeck, Carl A K, et al.
(författare)
-
Does endogenous glycosylation prevent the use of mouse monoclonal antibodies as cancer therapeutics?
- 1993
-
Ingår i: Immunology Today. - 0167-5699. ; 14:10, s. 477-479
-
Tidskriftsartikel (refereegranskat)abstract
- Monoclonal antibodies have many potential therapeutic benefits. However, when applied to humans, mouse monoclonal antibodies have several disadvantages. Here Carl Borrebaeck and colleagues describe a strategy to overcome the anti-Gal activity, thought to be one of the reasons why mouse mAbs have a limited half-life.
|
|
| 16. |
- Borrebaeck, Carl A K, et al.
(författare)
-
Kinetic analysis of recombinant antibody-antigen interactions : Relation between structural domains and antigen binding
- 1992
-
Ingår i: Bio/Technology. - : Springer Science and Business Media LLC. - 0733-222X. ; 10:6, s. 697-698
-
Tidskriftsartikel (refereegranskat)abstract
- The relation between domain structures of recombinant monoclonal antibody fragments and their reaction kinetics was studied for the first time using a novel biosensor based on surface plasmon resonance technology. The association and dissociation rate constants of Fab, Fv and single domain (VH fragment) anti-lysozyme antibodies were determined and compared to the intact monoclonal antibody. Fab and Fv fragments showed similar reaction kinetics and had affinity constants of 6 X 109 M-1 and 25 X 109 M-1, respectively. The single domain antibody had significantly different reaction kinetics compared to the fragments consisting of paired heavy and light chain domains. The VH domain had both a higher dissociation and a lower association rate constant, which resulted in an affinity constant approximately 250 times lower than the Fab fragment. This rapid evaluation of antibody reaction kinetics should prove to be an important selection parameter when comparing antibody fragments for their utility in therapeutic or other applications.
|
|
| 17. |
- Brew, Bronwyn K., et al.
(författare)
-
Maternal mental health disorders and offspring asthma and allergic diseases : The role of child mental health
- 2024
-
Ingår i: Pediatric Allergy and Immunology. - : Munksgaard Forlag. - 0905-6157 .- 1399-3038. ; 35:2
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Maternal psychological stress during pregnancy and postnatally has been shown to be associated with offspring atopic diseases (asthma, atopic dermatitis and allergic rhinitis). The aim of this study was to assess whether this association may be attributable to the child's own mental health disorders.METHOD: The study population included 15,092 twin children born 2002-2010 in Sweden. Questionnaire data at age 9 years was linked to national patient- and prescription registers. Maternal mental health during pregnancy and 3 years postnatally were identified from diagnosis and medication data (depression, anxiety and stress disorders). Atopic diseases in children were identified from questionnaires, diagnosis and medication data. Child mental health status (depression and anxiety) was identified from questionnaires. Three-way decomposition methods tested for mediation or interaction by child mental health disorders.RESULTS: Maternal mental health disorders were associated with most child atopic diseases including asthma aRR1.36 (95% CI 1.12, 1.60), and child mental health disorders, aRR1.73 (95% CI 1.56, 1.92). Children with mental health disorders were comorbid for atopic diseases with only asthma reaching statistical significance, aRR1.29 (95% CI 1.14, 1.47). Three-way decomposition found that mediation or interaction by child mental health disorders did not account for the mother mental health and child atopy associations except in parent-report asthma, where child mental health disorders mediated 13.4% (95% CI 2.1, 24.7) of the effect, but not for objectively defined (diagnosis and medication) asthma.CONCLUSION: The associations between maternal mental health and child asthma and allergic diseases do not appear to be attributable to child mental health disorders.
|
|
| 18. |
- Brorson, Håkan, et al.
(författare)
-
Controlled compression and liposuction treatment for lower extremity lymphedema.
- 2008
-
Ingår i: Lymphology. - 0024-7766. ; 41:2, s. 52-63
-
Tidskriftsartikel (refereegranskat)abstract
- In 1987 we noticed excess adipose tissue in a patient with arm lymphedema and later, objective studies confirmed this clinical finding in patients with non-pitting arm lymphedema following breast cancer. A prospective study was begun in 1993, and its long-term results (15 years) shows overall complete reduction of the excess volume in patients with non-pitting arm lymphedema and that adipose tissue dominates the excess volume. Encouraged by these results we operated on a patient with primary and secondary elephantiasis of the leg. The edema was first transferred from a pitting to a non-pitting state by controlled compression therapy. Then liposuction was performed to remove the remaining excess adipose tissue, and complete reduction was finally achieved. The patient wears compression garments continuously and during the 11 years of followup, no recurrence has occurred. This paper explains our philosophical approach: a pitting lymphedema first should be treated conservatively to remove excess fluid, then liposuction can be performed to remove remaining excess volume bothersome to the patient.
|
|
| 19. |
|
|
| 20. |
- Brorson, Håkan, et al.
(författare)
-
Suction-assisted lipectomy
- 2015
-
Ingår i: Lymphedema : Presentation, Diagnosis, and Treatment - Presentation, Diagnosis, and Treatment. - Cham : Springer International Publishing. - 9783319144924 - 9783319144931 ; , s. 313-324
-
Bokkapitel (refereegranskat)abstract
- 39.Brorson H, Svensson B, Ohlin K. Suction-Assisted Lipectomy. In: Greene AK, Slavin S, Brorson H, editors, Lymphedema - Presentation, Diagnosis, and Treatment. Cham, Switzerland: Springer; 2015: p. 313-324.
|
|
| 21. |
- Brorson, Håkan, et al.
(författare)
-
Volume measurements and follow-up
- 2015
-
Ingår i: Lymphedema : Presentation, Diagnosis, and Treatment - Presentation, Diagnosis, and Treatment. - Cham : Springer International Publishing. - 9783319144924 - 9783319144931 ; , s. 115-122
-
Bokkapitel (refereegranskat)
|
|
| 22. |
- Chin, L. T., et al.
(författare)
-
Site-directed primary in vitro immunization : Production of HIV-1 neutralizing human monoclonal antibodies from lymphocytes obtained from seronegative donors
- 1994
-
Ingår i: Immunology. - 0019-2805. ; 81:3, s. 428-434
-
Tidskriftsartikel (refereegranskat)abstract
- The design of an in vitro immunization system based on a synthetic heterotope immunogen, which was a peptide containing both T- and B-cell epitopes, that elicited a neutralizing, primary human humoral immune response against the human immunodeficiency virus (HIV-1) is reported here. This heterotope construct contained the major neutralizing B-cell epitope, within the V3 region of glycoprotein 120 (gp120), linked to a promiscuous helper T- cell epitope of tetanus toxin. The peptide was used to induce a human humoral in vitro immune response against the V3 region, using lymphocytes obtained from healthy, sero-negative blood donors. The in vitro immunized peripheral blood lymphocytes were Epstein-Barr virus infected and the antibody response to the synthetic peptide was evaluated using a solid-phase ELISA with the recombinant C-terminal fragment of gp120 (pB1, amino acid residues 287 467, derived from the HIV-1 LAI isolate). The heterotope construct yielded a significant frequency of specifically immunized B cells, in contrast to the control immunizations with individual T and B epitopes mixtures of these epitopes or no immunogen at all. This approach allowed us to generate human monoclonal antibodies, using lymphocytes derived from sero-negative donors, that cross-neutralized several HIV-1 strains, inhibited syncytia formation as well as prevented spreading of the viral infection from cell to cell. Thus, site-directed in vitro immunization using synthetic heterotopes might prove valuable in the dissection and induction of a protective humoral immune response.
|
|
| 23. |
- Cruz, Silian, et al.
(författare)
-
Mouse monoclonal antibodies against outer membrane proteins of a vaccine strain of Neisseria meningitidis B : 4:P1.15
- 1998
-
Ingår i: Minerva Biotecnologica. - 1120-4826. ; 10:2, s. 65-70
-
Tidskriftsartikel (refereegranskat)abstract
- Background. Neisseria meningitidis (Nm) is a Gram negative diplococcus causing bacterial meningitis and fulminant septicemia. In order to allow efficient characterization of infecting strains, antibody reagents for use as analytical tools have proven to be invaluable tools. Similarly, antibodies against relevant bacterial antigens may guide in the selection of components to be included in developing vaccine strategies. Methods. We have thus developed mouse monoclonal antibodies specific for class 1, 3 and 5 antigens expressed by the B:4:P1.15 isolate CU385/83, also being used in a recently developed protective vaccine. In particular, two antibodies CB-Nm.1 and CB- Nm.2 recognize epitopes partly overlapping the subserotype (class 1 antigens) and serotype (class 3 antigen) specificities detected by the previously defined antibodies C6 and 15-1-P4 respectively, were evaluated. Results. As judged by strain recognition, the absolute requirement for binding differs between both the class 1-specific and class 3 specific antibodies suggesting the importance of using multiple antibodies when evaluating subserotype/serotype characteristics of clinical isolates of Nm by serological methods. Conclusion. Furthermore, the development of antibodies crossreactive with subserotype/serotype antigens may partly explain the ability of outer membrane protein vaccine to induce protective activity against strains considered as carrying different class 1 and 3 antigens as determined by available (sub)serotyping reagents.
|
|
| 24. |
- De Cossío, Maria E Fernández, et al.
(författare)
-
Human monoclonal antibodies against an epitope on the class 5c outer membrane protein common to many pathogenic strains of Neisseria meningitidis
- 1992
-
Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 166:6, s. 1322-1328
-
Tidskriftsartikel (refereegranskat)abstract
- Neisseria meningitidis is a causative agent of meningitis. Despite vaccination programs, it still causes a large number of deaths in young children. Early diagnosis followed by passive immunization with human monoclonal antibodies could be an approach to effective therapy. Peripheral blood lymphocytes from normal, healthy blood donors and from vaccinated individuals were immunized in vitro, using outer membrane proteins purified from A. meningitidis B:4:P1,15. The immunized human B cells were Epstein-Barr virus transformed and fused to a heteromyeloma. Several stable human hybridoma cell lines were established and two, secreting antibodies against the 31-kDa class 5c outer membrane protein, were characterized further. The human antibodies were of IgG1 and IgG3 isotypes, with κ light chains. The recognized epitope was commonly found among pathogenic strains of N. meningitidis; thus, these human monoclonal antibodies may be important in the evaluation of N. meningitidis infections.
|
|
| 25. |
- Dueñas, M., et al.
(författare)
-
A point mutation in a murine immunoglobulin V-region strongly influences the antibody yield in Escherichia coli
- 1995
-
Ingår i: Gene. - 0378-1119. ; 158:1, s. 61-66
-
Tidskriftsartikel (refereegranskat)abstract
- Recombinant DNA technology has made it possible to produce specific Fab and scFv antibody (Ab) fragments in prokaryotic host cells. Using vectors designed for periplasmic expression of encoded Ab fragments, we have been studying how the sequence and genetic localization of the light chain (L-chain) variable region gene of a mouse Ab (CB-Nm.1) determined the level of Ab production. The variable region was shown to belong to the VKV family and contained a previously unreported Ile72. Nine different Ab constructions were tested in monocistronic (scFv) or dicistronic (Fab) operons for their ability to affect the synthesis level of the L-chain. When the gene coding for the L-chain was located downstream from the Fd fragment gene, the substitution of codons encoding Ile by a codon encoding Thr was found to be crucial for any expression of the L-chain fragment. This was, however, not accompanied by an increase in L-chain-specific mRNA, neither was there any change in the size of the mRNA. The fact that the unmutated L-chain protein was produced from cells transformed with certain other constructions indicated that the protein as such was not incompatible with the prokaryotic environment. Together, this suggested that the translation process was involved in the restricted production of the L-chain. Thus, surprisingly small substitutions significantly affected the expression level, a fact that will have important implications on the library size expressed in prokaryotic hosts, including phagedisplayed Ab libraries.
|
|
| 26. |
- Dueñas, M., et al.
(författare)
-
In vitro immunization of naive human B cells yields high affinity immunuglobulin G antibodies as illustrated by phage display
- 1996
-
Ingår i: Immunology. - 0019-2805. ; 89:1, s. 1-7
-
Tidskriftsartikel (refereegranskat)abstract
- In vitro antibody responses to a synthetic immunogen, consisting of both a B cell [V3 loop of gp120 from human immunodeficiency virus type 1 (HIV-1)] and a T-helper epitope (15 amino acids of tetanus toxoid) was studied. The in vitro activation was performed by primary and secondary in vitro immunizations, using lymphocytes obtained from uninfected, seronegative donors. Analysis of the in vitro immune response demonstrated an antigen-specific isotype switch, which was dependent on the presence of antigen-specific T-helper cells, CD40 ligation and antigen. Antibody libraries were constructed from cells derived directly from the naive donors, or from primary or secondary in vitro immunized B cells. Five libraries were displayed on filamentous phage and selected for anti-V3-specific Fab fragments, using a selection approach that linked recognition and phage replication. A panel of 19 recombinant antigen-specific Fab, representing different phases of the humoral in vitro immune response, were sequenced, expressed and analysed using a biosensor. Recombinant Fab fragments derived from cultures on day 12 exhibited an increase in affinity of close to two orders of magnitude compared to those obtained from cells primary immunized for 7 days. This study provides the first evidence that an antigen-specific in vitro immune response can yield high-affinity immunoglobuling G antibodies.
|
|
| 27. |
- Duenas, M., et al.
(författare)
-
Intra- and extracellular expression of an scFv antibody fragment in E. coli : Effect of bacterial strains and pathway engineering using GroES/L chaperonins
- 1994
-
Ingår i: BioTechniques. - 0736-6205. ; 16:3, s. 476-480
-
Tidskriftsartikel (refereegranskat)abstract
- We have studied the influence of bacterial host on the secretion of single-chain Fv antibody fragment (scFv), the production of this antibody fragment as intracellular fusion protein, and the effect of chaperonin coexpression on intracellular antibody expression. Seven bacterial strains were transformed with a vector carrying the genes encoding the variable regions of an anti-CEA scFv antibody and the ompA leader sequence (ptrp/ompA/scFvCEA). Expression and secretion of this antibody fragment were highest in the W3110 strain, as determined by Western blot analysis and enzyme immunoassay, where the scFv fragment amounted to approximately 30% of the total periplasmic protein. Except for BMH71-18, the other strains were unsuitable for antibody fragment expression, suggesting screening of bacterial strains as an important parameter. For intracellular expression, the scFv was expressed as a fusion protein with a 26-amino acid N-terminal fragment of human interleukin-2 (IL-2), using the pIL-2f/scFvCEA vector. The fusion protein was expressed at 30% of total biomass and retained antigen binding after in vitro refolding. Co-expression of chaperonin encoding plasmic pGroES/L with pIL-2f/scFv increased the intracellular production of the fusion protein two-fold, with a similar increase in the final amount of active scFv antibody fragment that could be obtained after in vitro refolding. The chaperonins had no effect on secretion of scFv antibody fragments, using the ptrp/ompA/scFvCEA.
|
|
| 28. |
- Dueñas, Marta, et al.
(författare)
-
Selection of phage displayed antibodies based on kinetic constants
- 1996
-
Ingår i: Molecular Immunology. - : Elsevier BV. - 0161-5890. ; 33:3, s. 279-285
-
Tidskriftsartikel (refereegranskat)abstract
- The display of antibody fragments on the surface of filamentous bacteriophages and the selection of binders from antibody libraries have provided powerful tools to generate human antibodies. We reported recently a new concept (SAP system) for the selection of specific phages by linking antigenic recognition and phage replication, using a soluble fusion protein containing the antigen and a fragment of the M13 coat protein 3. In this investigation, a model library has been composed using six different antibody fragments which were characterized individually regarding their k(ass), k(diss) and K(a). All Feb fragments were specific for a 15 amino acid region of the V3 loop of gp120 (HIV-1). We demonstrated that the SAP system could discriminate between the kinetic parameters of each clone, using different selection strategies. Phages expressing high affinity clones were selected preferentially using low doses of antigen but clones of lower affinity also could be selected by increasing the antigen concentration or using a preselection procedure. Phages expressing antibody fragment with high association or low dissociation rate constants were retrieved by utilizing short contact times between antigen and antibody or antigen-chase conditions.
|
|
| 29. |
- Eickmann, M., et al.
(författare)
-
Effect of cysteine substitutions on dimerization and interfragment linkage of human cytomegalovirus glycoprotein B (gp UL55)
- 1998
-
Ingår i: Archives of Virology. - : Springer Science and Business Media LLC. - 0304-8608 .- 1432-8798. ; 143:10, s. 1865-1880
-
Tidskriftsartikel (refereegranskat)abstract
- Experiments were carried out to analyze the function of cysteine residues at amino acid positions 506 (cI), 550 (cII), 573 (cIII), and 610 (cIV), in dimerization and/or disulfide linkage of human cytomegalovirus (HCMV) glycoprotein B (gB). Single c-codons or pairs were substituted in the gB sequence of constructs which were used for transfection and selection of stable transfectants. Analysis of gB expression products revealed that single substitutions of cIII or cIV, but neither single nor double substitutions of cI or/and cII prevented gB dimerization. All substituted gB derivatives were, however, no longer processed by proteolytic cleavage. After deletion of the membrane anchor domain, correct proteolytic processing was again observed for anchorless gB forms. Substitutions of cI or cI/cII in secretory gB appeared to interfere with disulfide linkage between gB cleavage fragments. In the case of anchorless gB with substitutions of cII, cIII, or cIII/cIV, however, extracellular gB forms were not recovered. Using the Sindbis expression system recovery of all anchorless gB forms with cysteine substitutions was achieved. Analysis verified involvement of cI/II substitutions in intrachain disulfide linkage between cleavage fragments of HCMV gB.
|
|
| 30. |
- Faber, Catherine, et al.
(författare)
-
Three-dimensional structure of a human Fab with high affinity for tetanus toxoid
- 1998
-
Ingår i: Immunotechnology. - 1380-2933. ; 3:4, s. 253-270
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The wide range of antibody specificity and affinity results from the differing shapes and chemical compositions of their binding sites. These shapes range from discrete grooves in antibodies elicited by linear oligomers of nucleotides and carbohydrates to shallow depressions or flat surfaces for accommodation of proteins: peptides and large organic compounds. Objectives: To determine the Fab structure of a high-affinity human antitoxin antibody. To explore structural features which enable the antibody to bind to intact tetanus toxoid, peptides derived from the sequence of the natural immunogen and antigenic mimics identified by combinatorial chemistry. To explain why this Fab shows a remarkable tendency to produce crystals consistently diffracting to d spacings of 1.7-1.8 Å. To use this information to engineer a strong tendency to crystallize into the design of other Fabs. Study design: The protein was crystallized in hanging or sitting drops by a microseeding technique in polyethylene glycol (PEG) 8000. Crystals were subjected to X-ray analysis and the three-dimensional structure of the Fab was determined by the molecular replacement method. Interactive computer graphics were employed to fit models to electron density maps, survey the structure in multiple views and discover the crystal packing motif of the protein. Results: Exceptionally large single crystals of this protein have been obtained, one measuring 5 x 3 x 2 mm (l x w x d). The latter was cut into six irregular pieces, each retaining the features of the original in diffracting to high resolution (1.8 Å) with little decay in the X-ray beam. In an individual Fab, the active site is relatively flat and it seems likely that the protein antigen and derivative peptides are tightly held on the outer surface without significant penetration into the interior. There is no free space to accommodate even a dipeptide between V(H) and V(L). One of the unique features of the B7-15A2 Fab is a large aliphatic ridge dominating the center of the active site. The CDR3 of the H chain contributes significantly to this ridge, as well as to adjoining regions projected to be important for the docking of the antigen. Both the ease of crystallization and the favorable diffraction properties are mainly attributable to the tight packing of the protein molecules in the crystal lattice. Discussion: The B7-15A2 active site provides a stable and well defined platform for high affinity docking of proteins, peptides and their mimotopes. The advantages for future developments are suggested by the analysis of the crystal properties. It should be possible to incorporate the features promoting crystallization, close packing and resistance to radiation damage into engineered human antibodies without altering the desired specificities and affinities of their active sites.
|
|
| 31. |
- Fritzell, Peter, et al.
(författare)
-
Cost-effectiveness of lumbar fusion and nonsurgical treatment for chronic low back pain in the Swedish lumbar spine study : A multicenter, randomized, controlled trial from the Swedish Lumbar Spine Study Group
- 2004
-
Ingår i: Spine. - : Lippincott Williams & Wilkins. - 0362-2436 .- 1528-1159. ; 29:4, s. 421-434
-
Tidskriftsartikel (refereegranskat)abstract
- Study Design. A cost-effectiveness study was performed from the societal and health care perspectives. Objective. To evaluate the costs-effectiveness of lumbar fusion for chronic low back pain (CLBP) during a 2-year follow-up. Summary of Background Data. A full economic evaluation comparing costs related to treatment effects in patients with CLBP is lacking. Patients and Methods. A total of 284 of 294 patients with CLBP for at least 2 years were randomized to either lumbar fusion or a nonsurgical control group. Costs for the health care sector ( direct costs), and costs associated with production losses ( indirect costs) were calculated. Societal total costs were identified as the sum of direct and indirect costs. Treatment effects were measured using patient global assessment of improvement, back pain ( VAS), functional disability (Owestry), and return to work. Results. The societal total cost per patient ( standard deviations) in the surgical group was significantly higher than in the nonsurgical group: Swedish kroner (SEK) 704,000 ( 254,000) vs. SEK 636,000 ( 208,000). The cost per patient for the health care sector was significantly higher for the surgical group, SEK 123,000 ( 60,100) vs. 65,200 ( 38,400) for the control group. All treatment effects were significantly better after surgery. The incremental cost-effectiveness ratio ( ICER), illustrating the extra cost per extra effect unit gained by using fusion instead of nonsurgical treatment, were for improvement: SEK 2,600 ( 600 - 5,900), for back pain: SEK 5,200 ( 1,100 - 11,500), for Oswestry: SEK 11,300 ( 1,200 - 48,000), and for return to work: SEK 4,100 ( 100 21,400). Conclusion. For both the society and the health care sectors, the 2-year costs for lumbar fusion was significantly higher compared with nonsurgical treatment but all treatment effects were significantly in favor of surgery. The probability of lumbar fusion being cost-effective increased with the value put on extra effect units gained by using surgery.
|
|
| 32. |
- Furebring, Christina, et al.
(författare)
-
Evaluation of novel control elements by construction of eukaryotic expression vectors
- 1997
-
Ingår i: Gene. - 0378-1119. ; 188:2, s. 191-198
-
Tidskriftsartikel (refereegranskat)abstract
- A novel mammalian eukaryotic expression vector for the production of immunoglobulin heavy chain (IgH) genes has been designed. This expression vector contains the variable heavy chain (VH) promoter, the IgH intron enhancer (μE) and the IgH 3' enhancer (3'E). This construct, designated pTIF-1, was stably transfected into the myeloma cell line J558L. A fivefold increase in the expression level of a rearranged IgH gene was observed when using the pTIF-1 vector containing the 3'E compared to an expression vector lacking this enhancer. Interestingly, this positive effect on the expression level of the 3' enhancer appears to be position independent. The introduction of two recently identified Ig control elements, HS3 and HS4, to the vector cassette did not further elevate the expression level in the cell line tested. The pTIF-1 vector can be used for expression of any antibody specificity, using PCR amplification of the VDJ region of interest. Furthermore, the constant region can easily be exchanged, which further facilitates studies to dissect different effector functions of IgH constant genes.
|
|
| 33. |
- Furer, Sebastian O., et al.
(författare)
-
The Performance-Determining Role of Lewis Bases in Dye-Sensitized Solar Cells Employing Copper-Bisphenanthroline Redox Mediators
- 2020
-
Ingår i: Advanced Energy Materials. - : Wiley-VCH Verlagsgesellschaft. - 1614-6832 .- 1614-6840. ; 10:37
-
Tidskriftsartikel (refereegranskat)abstract
- Copper redox mediators have enabled open-circuit voltages (V-OC) of over 1.0 V in dye-sensitized solar cells (DSCs) and have helped to establish DSCs as the most promising solar cell technology in low-light conditions. The addition of additives such as 4-tert-butylpyridine (tBP) to these electrolytes has helped in achieving high solar cell performances. However, emerging evidence suggests that tBP coordinates to the Cu(II) species and limits the performance of these electrolytes. To date, the implications of this coordination are poorly understood. Here, the importance of Lewis base additives for the successful implementation of copper complexes as redox mediators in DSCs is demonstrated. Two redox couples, [Cu(dmp)(2)](+/2+)and [Cu(dpp)(2)](+/2+)(with dmp = 2,9-dimethyl-1,10-phenanthroline and dpp = 2,9-diphenyl-1,10-phenanthroline) in combination with three different Lewis bases, TFMP (4-(trifluoromethyl)pyridine), tBP, and NMBI (1-methyl-benzimidazole), are considered. Through single-crystal X-ray diffraction analysis, absorption, and(1)H-NMR spectroscopies, the coordination of Lewis bases to the Cu(II) centers are studied. This coordination efficiently suppresses recombination losses and is crucial for high performing solar cells. If, however, the coordination involves a ligand exchange, as is the case for [Cu(dpp)(2)](+/2+), the redox mediator regeneration at the counter electrode is significantly retarded and the solar cells show current limitations.
|
|
| 34. |
|
|
| 35. |
|
|
| 36. |
|
|
| 37. |
|
|
| 38. |
- Ifversen, P., et al.
(författare)
-
Effect of cell-derived growth factors and cytokines on the clonal outgrowth of EBV-infected B cells and established lymphoblastoid cell lines
- 1993
-
Ingår i: Human Antibodies and Hybridomas. - 0956-960X. ; 4:3, s. 115-123
-
Tidskriftsartikel (refereegranskat)abstract
- Epstein-Barr virus (EBV) is a potent inducer of polyclonal B lymphocyte proliferation and is widely used as a tool for the establishment of B cell lines producing human monoclonal antibodies. However, because of low transformability, low clonability, and the inherent instability of EBV-infected B cells, valuable antibody-producing B cells are often lost during this procedure. We have here examined various cell-derived cytokines for their ability to enhance both the cellular outgrowth of newly infected B cells and the clonability of infected B cells and lymphoblastoid cell lines. Our results show that the murine thymoma cell line EL-4 is superior to peripheral blood mononuclear cells in both cellular outgrowth and cloning experiments, whereas monocyte-derived factors and monocyte cell lines were less capable than peripheral blood mononuclear cells in enhancing cellular outgrowth and cloning. Furthermore, the human T cell hybridoma cell line MP6 that secretes a B cell growth and differentiation factor, recently identified as an isoform of thioredoxin, is also capable of stimulating EBV-infected B cells and lymphoblastoid cell lines. Co-cultivation of EBV-infected B cells with MP6 cells significantly enhanced the cloning efficiency at the 1 cell/well level. The present results also suggest that one potential role of the MP6-derived thioredoxin could be the up regulation of IL-6 receptor expression in EBV-infected B cells.
|
|
| 39. |
- Jirholt, P., et al.
(författare)
-
Exploiting sequence space : Shuffling in vivo formed complementarity determining regions into a master framework
- 1998
-
Ingår i: Gene. - 0378-1119. ; 215:2, s. 471-476
-
Tidskriftsartikel (refereegranskat)abstract
- A novel approach in molecular design is presented, where in vivo formed complementarity determining regions (CDR) from antibody genes were shuffled into a specific framework region. A synthetic gene library of soluble VH-fragments was created and the complexity of the library was determined by sequencing. The synthetic genes were diverse and contained random combinations of CDR from different germlines. All CDR were randomised in one step and by using in vivo formed CDR, the length, sequence and combination were varied simultaneously.
|
|
| 40. |
|
|
| 41. |
- Karlsson, M K, et al.
(författare)
-
Remodeling of the spinal canal deformed by trauma
- 1997
-
Ingår i: Journal of Spinal Disorders. - 0895-0385. ; 10:2, s. 157-161
-
Tidskriftsartikel (refereegranskat)abstract
- Computed tomography (CT) examinations and functional scores were evaluated in 28 patients with thoracolumbar fractures with intraspinal fragments, of whom 20 underwent operation. The cross-sectional area and the sagittal and frontal diameters of the spinal canal were measured after the injury, postoperatively, and at follow-up (mean, 6 years). The operative reduction significantly increased both diameter and area of the spinal canal. During follow-up, a further significant increase of the sagittal diameter and the area was noted, in both surgically and conservatively treated patients. There was no difference in remodeling between the groups. Six patients in the surgically treated group had neurologic deficits at admission, five had improved, and one remained unchanged at follow-up. The presence or absence of intraspinal fragments should not influence the treatment strategy per se in cases without neurologic signs.
|
|
| 42. |
|
|
| 43. |
|
|
| 44. |
- Kjeldgård, Linnea, 1985-, et al.
(författare)
-
Bicycle crashes and sickness absence - a population-based Swedish register study of all individuals of working ages
- 2019
-
Ingår i: Bmc Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 19
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundIn recent years, bicycle injuries have increased, yet little is known about the impact of such injures on sickness absence (SA) and disability pension (DP). The aim was to explore SA and DP among individuals of working ages injured in a bicycle crash.MethodA nationwide register-based study, including all individuals aged 16-64years and living in Sweden, who in 2010 had in- or specialized out-patient healthcare (including emergency units) after a bicycle crash. Information on age, sex, sociodemographics, SA, DP, crash type, injury type, and injured body region was used. We analyzed individuals with no SA or DP, with ongoing SA or full-time DP already at the time of the crash, and with new SA >14days in connection to the crash. Crude and adjusted odds ratios (OR) with 95% confidence intervals for new SA were estimated by logistic regression.ResultsIn total, 7643 individuals had healthcare due to a new bicycle crash (of which 85% were single-bicycle crashes). Among all, 10% were already on SA or full-time DP at the time of the crash, while 18% had a new SA spell. The most common types of injuries were external injuries (38%) and fractures (37%). The body region most frequently injured was the upper extremities (43%). Women had higher OR (1.40; 1.23-1.58) for new SA than men, as did older individuals compared with younger (OR 2.50; 2.02-3.09, for ages: 55-64 vs. 25-34). The injury types with the highest ORs for new SA, compared with the reference group external injuries was fractures (8.04; 6.62-9.77) and internal injuries (7.34; 3.67-14.66). Individuals with traumatic brain injury and injuries to the vertebral column and spinal cord had higher ORs for SA compared with other head, face, and neck injuries (2.72; 1.19-6.22 and 3.53; 2.24-5.55, respectively).ConclusionsIn this explorative nationwide study of new bicycle crashes among individuals of working ages, 18% had a new SA spell in connection to the crash while 10% were already on SA or DP. The ORs for new SA were higher among women, older individuals, and among individuals with a fracture.
|
|
| 45. |
|
|
| 46. |
|
|
| 47. |
- Löf-Ohlin, Zarah M., et al.
(författare)
-
Hypermethylation of promoter regions of the APC1A and p16(INK4a) genes in relation to prognosis and tumor characteristics in cervical cancer patients
- 2011
-
Ingår i: International Journal of Oncology. - : Spandidos Publications. - 1019-6439 .- 1791-2423. ; 39:3, s. 683-688
-
Tidskriftsartikel (refereegranskat)abstract
- Hypermethylation of the O(6)-MGMT, p14(ARF), p16(INK4a), RASSFIA and APC1A genes are unfavourable prognostic markers in colorectal cancer (CRC). We hypothesized that they could be related to prognosis also in cervical cancer. Methylation was studied in DNA extracts from surgical specimens of cancer tissue by novel pyrosequencing methods. In 109 patients (90 squamous cell carcinomas, 19 adenocarcinomas), we found that hypermethylation of the APC1A gene promoter occurred in 8.3% of patients, and of p16(INK4a) in 1.8%. APC1A hypermethylation was significantly related to more advanced FIGO stage of the tumor (P=0.013), larger tumor diameter (P=0.049) and distant recurrence-free survival (P=0.0007), but not with locoregional recurrence rate, age, HPV status, DNA ploidy, tumor grade or malignancy grading score. We conclude that methylation of the APC1A promoter in cervical cancer, as diagnosed by pyrosequencing, is significantly related to major biological characteristics of the tumor, and may be a new predictor of poor prognosis in cervical cancer.
|
|
| 48. |
- Löf-Ohlin, Zarah M., et al.
(författare)
-
Relative telomere length in patients with late-onset Alzheimer's dementia or vascular dementia
- 2008
-
Ingår i: NeuroReport. - London : Lippincott Williams and Wilkins. - 0959-4965 .- 1473-558X. ; 19:12, s. 1199-1202
-
Tidskriftsartikel (refereegranskat)abstract
- Telomeres generally shorten with age. An accelerated shortening of the telomeres has been linked to several age-related disorders. We hypothesized that the relative length of telomeres could discriminate between patients with late-onset Alzheimer's disease (AD) and vascular dementia (VaD). A quantitative real-time PCR method was used to calculate the relative telomere length in 76 age-matched and sex-matched, newly diagnosed late-onset AD or VaD patients recruited from our Memory Unit. No significant difference was found in the relative telomere length between AD and VaD cases neither in men (P=0.315) nor women (P=0.12). Thus, we could not confirm that the length of telomeres would predict which form of dementia, late-onset AD or VaD that develops.
|
|
| 49. |
- Malmborg, Ann-Christin, et al.
(författare)
-
Selection of binders from phage displayed antibody libraries using the BIAcore(TM) biosensor
- 1996
-
Ingår i: Journal of Immunological Methods. - : Elsevier BV. - 0022-1759. ; 198:1, s. 51-57
-
Tidskriftsartikel (refereegranskat)abstract
- In this report we show that phage displayed antibodies can be selected based on dissociation rate constants, using a BIAcore(TM) biosensor. To demonstrate the principle, two Fab phage stocks displaying antibodies specific for hen egg lysozyme or phenyloxazolone were mixed in a ratio of 1:10 and injected over the biosensor chip containing immobilized lysozyme. Antigen-specific bound phages were eluted and analysed for specificity and phage titer. This procedure enriched for phages carrying specific antibodies. Selection of high affinity binders from phage libraries was then demonstrated with the BIAcore(TM) when phages were eluted and collected at different time points. Soluble antibody fragments were subsequently expressed and their kinetic parameters were determined. The time of elution was directly proportional to the affinity, due to decreased dissociation rate constants. This procedure offers a rapid and simple approach for selecting binders from phage libraries differing in antibody dissociation rate constants.
|
|
| 50. |
- Nilsson, Nina, et al.
(författare)
-
Altered gene expression associated with apoptosis in a pre-B-leukemic cell line following cross-linking of MHC class I
- 1997
-
Ingår i: Experimental Cell Research. - : Elsevier BV. - 0014-4827. ; 231:1, s. 190-197
-
Tidskriftsartikel (refereegranskat)abstract
- The major histocompatibility complex class I (MHC-I) has recently been shown not only to present antigens to the immune system but also to mediate transmembrane signaling, resulting in activation, inactivation, or apoptosis. Such signaling has been observed in both normal and malignant cells of the B and T cell lineage. Cross-linking of MHC-I on the pre-B- acute-lymphocytic cell line KM-3 induces an apoptotic process, which becomes evident after approximately 12 h. In order to better understand the mechanisms regulating this apoptotic process, we have investigated both gene expression and the effect of cross-linking on certain intracellular events. Differential display PCR was used to isolate two gene fragments whose level of expression was associated with the induction of apoptosis as they were downregulated in KM-3 cells following MHC-I cross-linking. These genes encode novel molecules whose function remains to be elucidated. It was further demonstrated that the apoptotic process was not accompanied by changes in [Ca2+](i), the level of activation of NF-κB, or changes in protein kinase C activity and that the initiation of apoptosis could be prevented by phorbol ester treatment. It is thus suggested that multiple, fine-tuned molecular events determine the outcome of cross-linking of MHC-I in this pre-B-lymphocytic cell line.
|
|
