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E Möller

Publications and source records attributed to E Möller.

At least 73 records · Page 4Linked to original sources
PubMed1993

Partial biochemical characterization and purification of IgG2b inducing factor as a new cytokine from synovial fluid of patients with rheumatoid arthritis.

Rheumatoid arthritis synovial fluid (RA-SF) contains a novel biological activity, which selectively induces IgG2b antibody production in lipopolysaccharide (LPS)-activated mouse spleen cells in vitro and in vivo. Our previous studies have shown that this activity is not functionally identical to other well-known cytokines and interleukins. In this study we demonstrate the partial purification and biochemical characterization of the IgG2b inducing activity in RA-SF. Biochemical characterization revealed that the IgG2b inducing activity in RA-SF has the following properties: it is a protein, sensitive to pH > 11 and < 4, which is precipitated by 50% of saturated ammonium sulphate and has a molecular weight of 50-70 kDa; it binds to Cibacron-blue and heparin and its activity is not mediated by immunoglobulins or immune complexes, which are present in RA-SF. Biochemical characteristics of the IgG2b inducing activity also differ from other cytokines and interleukins. The term IgG2b inducing factor is proposed for this novel activity.

Arthritis, Rheumatoid↗
PubMed1993

CD13 (human aminopeptidase N) mediates human cytomegalovirus infection.

Human cytomegalovirus (HCMV) infects cells by a series of processes including attachment, penetration via fusion of the envelope with the plasma membrane, and transport of the viral DNA to the nucleus. The details of the early events of HCMV infection are poorly understood. We have recently reported that CD13, human aminopeptidase N, a metalloprotease, is present on blood cells susceptible in vitro to HCMV infection (C. Söderberg, S. Larsson, S. Bergstedt-Lindqvist, and E. Möller, J. Virol. 67:3166-3175, 1993). Here we report that human CD13 is involved in HCMV infection. Antibodies directed against human CD13 not only inhibit infection but also block binding of HCMV virions to susceptible cells. Compounds known to inhibit aminopeptidase activity block HCMV infection. HCMV-resistant murine fibroblasts have heightened susceptibility to HCMV infection after transfection with complementary DNA encoding human CD13. A significant increase in binding of HCMV was observed in the CD13-expressing transfectants compared with neomycin-resistant control mouse cells. However, murine fibroblasts transfected with mutant CD13, lacking a portion of the aminopeptidase active site, remained susceptible to HCMV infection. Thus, human CD13 appears to mediate HCMV infection by a process that increases binding, but its enzymatic domain is not necessary for infection.

3T3 Cells↗
PubMed1993

Definition of a subset of human peripheral blood mononuclear cells that are permissive to human cytomegalovirus infection.

The identity of cells responsible for transmission of human cytomegalovirus (HCMV) in blood products or bone marrow transplants is unknown. We have tested the capacity of HCMV to in vitro infect human peripheral blood mononuclear cells (PBMC) from healthy donors and found that certain PBMC are permissive to HCMV infection. In vitro-infected viable cells were double stained for surface expression of different HMCV proteins and for cell-type-specific antigens to allow the identification of sensitive cells. All analysis were performed on viable cells, using HCMV-specific monoclonal antibodies and automated flow cytofluorimetry. PBMC were infected either with the laboratory-adapted HCMV strain AD169 or with a virus isolate obtained from a viremic patient. Up to 25% of all PBMC could express the major immediate-early antigen as well as the pp65 antigen, known at the lower matrix protein. Infected cells were mainly CD14+ monocytes, but also a small population of large CD8+ cells were susceptible to HCMV infection. CD19+ B lymphocytes were resistant to HCMV infection. Different populations of infected cells were enriched by using Dynabeads coated with cell-type-specific antibodies, and the presence of infectious virus was demonstrated by incubating the selected and sonicated cell material on human fibroblasts. Only material from infected monocytes and from CD3+ CD8+ cells gave rise to HCMV-specific plaques. The presence of HCMV mRNA as a sign of active viral transcription of the major immediate-early and late pp150 genes in infected cells was demonstrated by using nested reversed polymerase chain reaction. A common denominator was found for all cells that could be infected with HCMV. The CD13 antigen, a 130- to 150-kDa integral membrane protein identical to the enzyme aminopeptidase N, was expressed on all HCMV-permissive cells.

Antigens, CD↗
PubMed1993

Identification of blood mononuclear cells permissive of cytomegalovirus infection in vitro.

We conclude that both the experimental strain Ad169 and a CMV isolate obtained from a patient could infect PBMCs in vitro. The identity of infected cells was established as CD14+ monocytes and a small population of CD3/CD8+ large granular lymphocytes. No evidence of sensitivity to infection was obtained in small lymphocytes, in either the B or T cell population. Furthermore, flow cytometric analysis of cells expressing CMV-encoded antigens is a sensitive assay, as is the demonstration of viral RNA using reversed PCR and nested primer pairs. Since three different types of analyses all indicated active production of structural CMV antigens in infected cells, we conclude that monocytes and some CD8+ large lymphocytes might serve as reservoirs for latent CMV infection and might be responsible for the transfer of CMV infection. Presently, it cannot be determined whether PBMCs are indeed sensitive to a primary infection. Direct sequencing of virus isolates from in vitro-infected cells will have to be carried out to settle this issue. However, we favor the explanation that CMV causes a primary in vitro infection, since, as discussed above, various activating substances can induce the expression of CMV-encoded antigens in blood cells from seropositive donors. Finally, we found that the presence of the CD13 marker was a common denominator of all cells sensitive to CMV infection. We are presently attempting to elucidate whether the CD13 molecule is instrumental in the infection of cells by CMV.

Antigens, CD↗
PubMed1992

Different genetic backgrounds for malnutrition-related diabetes and type 1 (insulin-dependent) diabetes mellitus in south Indians.

HLA-DRB, -DQA and -DQB genes were studied in ten South Indian malnutrition-related diabetic patients, ten Type 1 (insulin-dependent) diabetic patients and 45 control subjects, by TaqI restriction fragment length polymorphism analysis. The DR7,DQw9 haplotype was found to be frequent in patients with malnutrition-related diabetes (p less than 0.01). The DRw17,DQw2 haplotype was overrepresented in the patients with Type 1 diabetes compared to control subjects (p less than 0.05). In vitro amplification of the polymorphic second exon of DQB genes by the polymerase chain reaction technique was performed on DNA from 10 malnutrition-related diabetic patients, 10 Type 1 diabetic patients and 13 control subjects, as they belong to a new population. Hybridization with sequence-specific oligonucleotide probes for DQB1 alleles showed homozygosity of aspartic acid at position 57 in 7 of 10 malnutrition-related diabetic patients compared to 2 of 10 Type 1 diabetic (p less than 0.05) and 15 of 45 control subjects (p less than 0.05). Homozygosity of non-aspartic acid at position 57 was present in 7 of 10 Type 1 diabetic compared to 0 of 10 malnutrition-related diabetic patients (p less than 0.005) and 3 of 45 control subjects (p less than 0.05). This study has confirmed the association of DQB1 57 non-asp in South Indians with Type 1 diabetes. In addition, our data clearly show that the genetic background of malnutrition-related diabetes mellitus is different from that of Type 1 diabetes.

Diabetes Mellitus↗
PubMed1992

Specific and non-specific autoreactive immunity.

Most autoimmune diseases are HLA-associated which supports the notion that they are dependent upon specific immune activation of a limited set of T cell clones. Findings which imply that induction of autoimmune reactivity probably does not differ from normal immune responses are discussed. The possibility of transferring autoimmune disease using T cell clones indicates that target structures for auto-immune attack are also present in healthy individuals. In the present article, it is argued that autoimmune reactions and immunity against nominal conventional antigens in principle are effected and regulated by similar mechanisms. It is assumed that persistent tissue damage occurs if immune attack is directed against tissues that cannot be regenerated, such as in diabetes, or are only slowly reconstituted, such as in rheumatoid arthritis. Normal immune responses are regulated by various inflammatory mediators and cytokines/interleukins. The joint of patients with rheumatoid arthritis is discussed as a model for propagation of immune reactions and tissue destruction in autoimmune disease. Of the different cytokines which are present in the synovial fluid or produced by cells in the synovial tissue, most are presumed to have originated in macrophages/monocytes such as IL-1, IL-6, IL-8, TNF-alpha and TGF-beta. Even so, T cells are believed to have an important role for the continued reactivity associated with autoimmune disease. This discrepancy can be explained in different ways. T cell products might escape detection because they are short-lived, they are immediately consumed or they are produced only during short time intervals.(ABSTRACT TRUNCATED AT 250 WORDS)

Arthritis, Rheumatoid↗
PubMed1992

Rheumatoid arthritis synovial fluid enhances T cell effector functions.

Rheumatoid arthritis is a chronic autoimmune joint disease of unknown etiology. T cells are believed to be important in the pathogenesis of rheumatoid arthritis since they infiltrate the joints and express several activation markers, such as MHC class II and IL-2R. In this study we have elucidated the effect on freshly isolated T cells of rheumatoid arthritis synovial fluid (RA-SF), which contains in vivo produced cytokines and enzymes. The mouse mixed lymphocyte culture (MLC) has been used as a model and specific cytotoxicity was evaluated against 51Cr-labelled sensitive target cells. Studies have shown that RA-SF contains a B cell differentiation activity that can cross-react between the human and murine species. Here we have shown that the addition of RA-SF strongly potentiates cytotoxic activity as well as lymphokine production by allogeneic activated effector T cells. The enhanced cytotoxicity induced by RA-SF was found to be due to a combined effect of increased cytotoxic T lymphocyte (CTL) precursor frequency, measured by limiting dilution analysis, and a more efficient killing on a per cell basis. Kinetic studies show that RA-SF must be added within 48 h after initiation of the MLC, otherwise the effect is lost. The target cell specificity of RA-SF was studied, using enriched CD4+ or CD8+ responder cells in the MLC. It was found that RA-SF could act directly on the CD8+ cells and potentiate their development to cytotoxic effector cells: this activity was not found when CD4+ responder cells were used instead. RA-SF could, on the other hand, greatly enhance IL-2 production by CD4+ responder cells. We suggest that B and T cell activity in RA-SF is important in the propagation of chronic inflammation in the joints of patients with rheumatoid arthritis.

Animals↗
PubMed1992

Fewer acute rejection episodes and improved outcome in kidney-transplanted patients with selection criteria based on crossmatching.

Cross-matches performed on sera from presensitized patients have so far failed to differentiate clinically "relevant" from clinically "irrelevant" antibodies due to insufficient specificity characterization. In order to find a basis for such a possibility, 72 consecutive kidney transplanted patients were selected and studied retrospectively. Our policy has been to accept weakly positive (less than 50%) cytotoxicity on donor B splenic lymphocytes in the crossmatch test. Forty-six patients who had early acute rejections and 26 who had no acute rejections were selected for the study. Antibodies in current sera were characterized according to their target cell reactivity, immunoglobulin class, and HLA/non-HLA specificities. Crossmatches were performed using both the cytotoxicity and the flow cytometric method. We found that the factor that differentiates clinically "relevant" from clinically "irrelevant" antibodies is the HLA specificity of the lymphocyte-reactive antibodies. A high proportion of patients with posttransplant complications such as acute rejections had antibodies with specificities for HLA (particularly class I) antigens, while patients without rejections had either no detectable antibodies or antibodies reactive with non-HLA antigens only. In the present study, after elimination of false-positive reactions by ultracentrifugation of current sera, we found that flow cytometric crossmatches may not necessarily be more specific than the ordinary cytotoxicity crossmatch, since a positive flow cytometric crossmatch is often, but not always, associated with a weakly positive B cell cytotoxic crossmatch (10-25% reactivity). Antibodies causing a positive flow cytometric crossmatch could constitute low-titerd complement-fixing antibodies, non-complement-fixing antibodies, or both. Thus our study shows that it is possible to identify, prior to transplantation, patients with a risk of early posttransplant immunological complications such as acute rejection and to differentiate these from those who are more likely to have an uncomplicated posttransplant clinical course. A more careful patient selection based on adequate crossmatch testing, including specificity determination, might reduce the frequency of acute rejections and improve the outcome of transplantation.

Antibody Specificity↗
PubMed1992

The occurrence of cytotoxic and non-complement-fixing antibodies in the crossmatch serum of patients with early acute rejection episodes.

In an earlier study we found a strong correlation between the presence of donor-reactive HLA-specific antibodies in the crossmatch serum and early acute rejection episodes. Our experience was also that some of these antibodies were not cytotoxic and could therefore not be detected using the microcytotoxicity assays. In the present study, 11 patients from the earlier study who had weakly positive B cell reactive cytotoxic antibodies of the IgG class were further characterized. In addition, 14 new patients were selected who experienced early acute rejections but had a completely negative donor-B cell cytotoxicity crossmatch. A group of 12 controls without immunological complications was added, as well as 5 patients with early graft losses due to nonimmunological causes. Using the flow cytometric crossmatch test we confirmed the presence of HLA-specific antibodies in all 11 patients from the earlier study. In addition, positive flow cytometric crossmatches shown to be caused by HLA antibodies were observed in 11 of the 14 patients with acute rejections and negative cytotoxic crossmatch. One of 17 control patients had antibodies that were not HLA-reactive. IgA antibodies as well as IgG subclass determinations were performed in all positive sera. A substantial proportion of patients had HLA-specific antibodies of non-complement-binding classes (IgG2, IgG4, IgA) often of higher titers than IgG1 and IgG3. The subclass distribution pattern was heterogeneous and often included several subclasses. We conclude that non-complement-fixing antibodies can also contribute to the risk for development of early acute rejections after necrokidney transplantation. Immunological mechanisms for these findings are discussed.

Antibodies↗
PubMed1992

Occlusal control of mandibular elevator muscles.

Occlusal stability and mandibular elevator muscle function was studied in 25 women (20-30 yr of age). They had 27-32 fully erupted teeth with few treated occlusal surfaces, and craniomandibular function including mandibular mobility was normal. The aim was to analyze the influence of natural patterns of occlusal contact on electromyographic activity, unaffected by pain and functional disorders. Occlusal stability was assessed in the intercuspal and in lateral contact positions as the number of teeth with physical contact and the number of opposing pairs of teeth in contact. Electromyographic activity was recorded by surface electrodes over anterior and posterior temporalis and masseter muscles. In general, positive correlations were found between occlusal stability in intercuspal position and moderate to strong static and dynamic contractions, most significant in masseter muscles, indicating that forceful contraction of these muscles implies stable occlusion. Systematically, the duration of activity during chewing was negatively correlated with occlusal stability in the intercuspal position, most pronounced in working-side muscles. This pointed to shorter contractions with stable occlusion and is interpreted as the result of less need for stabilizing activity. It is concluded, that the correlations between occlusal stability and elevator muscle function are probably based on feedback mechanisms from periodontal pressoreceptors.

Adult↗
PubMed1992

Craniomandibular disorders and masticatory muscle function.

The heading craniomandibular disorders covers a wide range of abnormal and pathologic conditions accompanied by orofacial pain and impaired mandibular function, the masticatory muscles and the temporomandibular joints being the structures most frequently involved. Prevalences of severe craniomandibular disorders accompanied by headache and facial pain urgently in need of treatment are 1-2% in children, about 5% in adolescents, and 5-15% in adults, with higher values in women than in men. With respect to physiology and ergonomics, masticatory muscles are comparable to other human skeletal muscles, e.g. of shoulder, neck and lower back. Therefore these muscles share pathogenesis, symptoms and signs of muscular disorders caused by prolonged, low-level static contractions or intermittent isometric contractions at higher levels. Since the same elements of performance in the masticatory muscles are influenced by occlusal factors, they link the development of muscular fatigue, discomfort and pain to the dental occlusion. Furthermore, changes of the occlusal surfaces, e.g. due to dental treatment, may influence the performance of the masticatory muscles, and consequently interfere with local muscular function.

Adolescent↗
PubMed1991

[Identification of HLA class II polymorphism with molecular biology techniques].

All the biologically relevant HLA class II allelic variants can not be identified with conventional serological tissue typing techniques. During the past few years considerable advances have been made in HLA class II typing with molecular techniques now widely used in routine clinical tissue typing. The next few years are likely to see the development of tissue typing techniques based on the polymerase chain reaction (PCR), for use in acute transplantation. A new method for the rapid identification of genetic polymorphisms is described--allele-specific PCR amplification.

HLA-D Antigens↗
PubMed1991

Relationship between IgG2b-inducing activity in rheumatoid arthritis synovial fluid and other well-known cytokines and inflammatory mediators.

In the present study, we sought to identify the T cell-replacing factor which selectively induces IgG2b antibody formation in lipopolysaccharide-activated mouse spleen cells in vitro and in vivo, and which is present in the synovial fluid (SF) of rheumatoid arthritis (RA) patients. The protein A plaque assay was used to measure IgM, IgG1, IgG2b, and IgG3 plaque-forming cells. An enzyme-linked immunosorbent assay was used to measure interleukin-6 (IL-6) levels in RA SF. We found that IgG2b induction by RA SF is not caused by IL-6, IL-1, or any other inflammatory cytokines or mediators, such as transforming growth factor beta, platelet-derived growth factor, nerve growth factor, fibroblast growth factor, epidermal growth factor, elastase, collagenase, and phospholipase A2. IgG2b-inducing factor in RA SF has unique biological properties compared with those of the interleukins and inflammatory mediators known to be present in RA SF.

Antibodies, Anti-Idiotypic↗