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Biomedical subjects

E Möller

Publications and source records attributed to E Möller.

At least 109 records · Page 6Linked to original sources
PubMed1989

Survival and immunogenicity of dissociated allogeneic fetal neural dopamine-rich grafts when implanted into the brains of adult mice.

The survival of grafts of dissociated allogeneic fetal neural dopamine (DA) rich tissue in the striatum has been studied after transplantation between inbred strains of mice differing at defined immunogenetical loci between donor and recipient. Six to 7 weeks and 15 weeks after grafting, surviving grafted DA neurons were found in the brains of all the recipients, albeit with a large variation in numbers, located either within the striatum or within the adjacent lateral ventricle. The mean number of surviving DA neurons did not differ between the syngeneic controls and the histoincompatible donor-host combinations, and there was no difference in survival between grafts that differed at single or multiple major histocompatibility complex (MHC) loci, and those that differed at multiple non-MHC loci. The amount of inflammatory cells in the graft area did not differ between the groups, and none of the animals showed massive infiltration of inflammatory cells. The in situ immunogenicity of the grafted neural tissue after intracerebral implantation was monitored by means of Simonsen's alloimmunization test, at 6-7 weeks after transplantation, which provides a sensitive measure primarily of the cellular immunological response. Most, but not all, graft recipients showed immunization with a Spleen Index (S.I.) close to that seen in recipients of an orthotopical skin graft of the same histoincompatibility combination. In contrast to the prolonged survival of the intracerebral neural transplants, none of the skin grafts survived longer than 3 weeks, thus demonstrating the immunologically privileged status of the brain. We conclude that intracerebrally grafted allogeneic neural tissue is capable of provoking a cellular immune response. Despite host immunization, however, the dissociated fetal neural allografts survived for at least 15 weeks without any overt signs of rejection, regardless of the donor-host combination used.

Animals↗
PubMed1989

[Online patent searching--rapid responses to critical questions].

Online searching in publically available patent files opens up interesting possibilities to provide a rapid response to critical questions. A computerized analysis of all patents of leading German pharmaceutical companies over the last decade in important indication areas is described. Supported by subsequent manual processing of individual patents it is shown that duplicate experiments on animals practically never occur.

Chemical Phenomena↗
PubMed1989

Primarily chronic progressive and relapsing/remitting multiple sclerosis: two immunogenetically distinct disease entities.

HLA class II gene polymorphism was investigated in 100 patients with clinically definite multiple sclerosis (MS) by restriction fragment length polymorphism analysis of Taq I-digested DNA using DRB, DQA, and DQB cDNA probes. Twenty-six patients had primarily chronic progressive MS and 74 had relapsing/remitting MS. The latter group included patients with a secondary progressive evolution of symptoms. Both clinical forms of MS were found to be associated with the DRw15,DQw6 haplotype. In addition, primarily chronic progressive MS was positively associated with the DQB1 restriction fragment pattern seen in DR4,DQw8, DR7,DQw9, and DRw8, DQw4 haplotypes, as well as negatively associated with the Taq I DQB1 allelic pattern corresponding to the serological specificity DQw7. Relapsing/remitting MS was positively associated with the DQB1 allelic pattern observed in the DRw17,DQw2 haplotype. These three DQB1 alleles are in strong negative linkage disequilibria with DRw15. The two susceptibility markers of each clinical form of MS act additively in determining the genetic susceptibility, as the relative risks for individuals carrying both markers roughly equal the sum of respective risks. Different alleles of the DQB1 locus defined by restriction fragment length polymorphisms contribute to susceptibility and resistance to primarily chronic progressive MS as well as to susceptibility to relapsing/remitting MS. The observed immunogenetic heterogeneity between the different clinical forms of MS favors the hypothesis that primarily chronic progressive MS and relapsing/remitting MS are two distinct disease entities.

Alleles↗
PubMed1989

Synovial fluid from rheumatoid arthritis patients induces polyclonal antibody formation in vivo.

Our previous studies demonstrated the presence of a T-cell replacing factor in the synovial fluid (SF) of patients with rheumatoid arthritis (RA) and that RA-SF can activate, selectively, the induction of IgG2b antibody secreting cells in lipopolysaccharide (LPS)-pretreated mouse spleen cell cultures. In the present study the effect of RA-SF was tested in vivo in mice. Injection of the polyclonal activator LPS induced the production of IgM and IgG3 secreting cells in normal mice. However, the addition of RA-SF led to a selective increase in the production of IgG2b with a peak response on day 5 and IgG1 plaque-forming cells (PFC) with a peak on day 7. Neither the IgG2b nor IgG1 responses were caused by specific immunity against heterologous proteins present in RA-SF, as injection of in vitro inactive RA-SF samples did not induce PFC. The effect on B cells of RA-SF was further evaluated by injection of RA-SF in combination with LPS to the Xid B-cell deficient CBA/N mice. RA-SF had identical effects in CBA/N as in normal mice. The biological implication of these findings is discussed. Our earlier results support the idea that B cells are endogenously activated in RA patients. We have speculated that this activation is caused by the B-cell differentiation factor which is present in SF. Therefore, we also tested whether RA-SF could influence antibody-forming cells in mice that spontaneously develop autoimmunity. We found that injection of RA-SF alone, in the absence of any other activating substance, induced a very marked increase of IgG producing cells in (NZW x NZB) F1 hybrid mice. From a relatively high background level the RA-SF could still induce an up to 100-fold increase in the numbers of PFC in spleens of such mice.

Animals↗
PubMed1989

Rheumatoid synovial fluid reconstitutes the B-cell defect in CBA/N mice.

Synovial fluid from patients with rheumatoid arthritis (RA-SF) contains a biological activity which can replace T cells for activation of antibody secretion in human blood lymphoid cells and which can also induce the selective differentiation of IgG2b-secreting cells in lipopolysaccharide (LPS)-pre-activated mouse spleen cells. The B-cell activity of this factor was studied in CBA/N mice which have an X-linked B-cell immunodeficiency which manifests itself as a defective humoral response to certain thymus-independent antigens (TI-2). RA-SF has now been shown to reconstitute partly the B-cell deficiency in CBA/N splenic B cells in vitro. Addition of RA-SF to LPS-pretreated cell cultures results in IgG2b secretion in CBA/N spleen cells as well. In contrast to cells from normal CBA mice, cells from CBA/N mice cannot respond to interleukin 4 (IL-4) after addition of LPS with production of IgG1 antibodies in vitro. However, the addition of RA-SF completely restores a normal IL-4-induced IgG1 response. No other biologically active factors have been shown to allow the production of IgG antibody producing cells in CBA/N splenic B cells. It is postulated that the xid immunodeficiency could be the result of a deficient production of a biological activity which is abundant in RA-SF.

Animals↗
PubMed1989

Specificity of HLA restricting elements for human nickel reactive T cell clones.

In order to study the fine specificity of HLA class II restriction, we have established nickel specific T cell clones from a nickel allergic patient. Cells were cloned by limiting dilution after primary stimulation and selection of nickel specific blasts. Several clones were established which were all shown to carry the CD4 marker. All clones were shown to be completely blocked by monoclonal antibodies directed against DR antigens, but unaffected by antibodies against DQ or DP, thus demonstrating their DR specificity. For the study of HLA class II restriction, a panel of cell donors was carefully HLA typed by including the use of DRB and DQB cDNA probes. Specificity analysis, using allogeneic antigen presenting cells, revealed that the clones were either restricted to DR3- or DR4-like molecules, which is consistent with the fact that the donor was DR3, DR4 positive. However, the studies also revealed that the fine specificity of the DR3 and DR4 restriction could not be completely assessed by serological and genomic typing of panel cells. This indicates that cellularly defined HLA restriction elements recognized by T cells cannot be defined properly with available class II typing methods, and the results of these experiments documented the additional polymorphism of class II restriction elements. The clonal specificity analysis has shed further light on the biologically relevant level of DR polymorphism.

Clone Cells↗
PubMed1989

Individuals with HLA-DR blank alleles display well-known DR-DQ RFLPs.

We have characterized HLA-DRB, -DQA, and -DQB gene polymorphism in a large number of serologically DR blank haplotypes with the restriction enzymes Taq I, Bam HI, and Pvu II, with the aim of finding new RFLPs in the Caucasian population. Locus-specific RFLPs were combined for a definition of Taq I DR-DQ haplotypes. All observed DNA haplotypes could be found in a control group of 100 individuals, but with a different distribution. Serologically less well-defined specificities were over-represented in the blank group, in particular the DRw13-associated Taq I DR-DQ haplotype T-13.3. We conclude that the majority of DR blank haplotypes are probably closely related or identical to previously defined DR alleles. The extent of DR polymorphism in the Caucasian population seems to be well mapped, considering the extremely small proportion of rare Taq I DR-DQ haplotypes and lack of new patterns in this study.

Alleles↗
PubMed1989

Clinical significance of isometric bite force versus electrical activity in temporal and masseter muscles.

Bite force and activity in temporal and masseter muscles during biting and chewing were recorded in 19 control subjects and 23 subjects with symptoms and signs of functional disorders of the craniomandibular system. The entire group comprised 13 men and 29 women, 14-63 yr of age. Maximal unilateral bite force was 480 Newton (N) in control subjects and 387 N in patients, with corresponding bilateral values of 347 N and 230 N. At predetermined levels of contraction, temporalis and masseter activity were linearly related. Correlations of bite force and activity in short static contractions were significant with respect to unilateral, but not to bilateral force measurements. Only in the masseter muscle was strength of dynamic contractions during chewing significantly correlated to bite force. With the present method it was demonstrated that unilateral bite force is a simple clinical indicator of mandibular elevator strength as a whole, but inadequate to disclose asymmetric conditions. During isometric contraction, relative strength of electromyographic activity fairly accurately imaged the output of mechanical activity.

Adolescent↗
PubMed1988

A DR4-associated DR-DQ haplotype is significantly associated with rheumatoid arthritis.

Forty-three patients with seropositive, erosive rheumatoid arthritis (RA) and 24 members of 5 RA multicase families were studied for HLA class II gene polymorphism, using restriction fragment analysis with complementary DNA probes for DR beta and DQ beta chains. This method generates HLA-DR-DQ haplotypes that are highly correlated with HLA-DR serology. Thirty-five of the 43 RA patients (81%) were positive for one or for both of the DR4-associated DR-DQ haplotypes, 4.1 and 4.2. Among these patients, the 4.1 haplotype was found significantly more often than in DR4+ controls (P less than 0.01). The haplotype segment C3;B15;DR4 was present in all RA patients in 4 of the 5 families, and included the DR-DQ4.1 haplotype.

Adult↗
PubMed1988

HLA-B27: an important genetic risk factor for lone aortic regurgitation and severe conduction system abnormalities.

PURPOSE: HLA-B27, an immunogenetic marker that is present in 8 percent of the white population around the world, has been found to be an important risk factor for the development of a group of rheumatic disorders, the seronegative spondyloarthropathies. Our objective was to assess the possible role of HLA-B27 and the associated inflammatory disease process in the development of lone aortic regurgitation. PATIENTS AND METHODS: A group of 91 patients with lone aortic regurgitation were studied by HLA typing and clinical and roentgenologic examination. RESULTS: The HLA-B27-associated inflammatory disease process was found to be the probable underlying cause in 15 to 20 percent of patients with lone aortic regurgitation of different degrees of severity. Furthermore, HLA-B27 was found in 88 percent of the male patients with the combination of aortic regurgitation and severe conduction system abnormalities. CONCLUSION: We suggest that this cardiac syndrome should be regarded as an HLA-B27-associated syndrome, sometimes part of ankylosing spondylitis or Reiter's disease, but just as often presenting without obvious rheumatic disease. The marker is thus an important and widely distributed risk factor not only for the development of rheumatic disease but also for acquired aortic regurgitation and sever conduction system abnormalities.

Aortic Valve Insufficiency↗
PubMed1988

Biological characterization of T cell-replacing factor in the synovial fluid of rheumatoid arthritis patients.

The synovial fluid of patients with rheumatoid arthritis (RA) contains a biologically active factor which has the ability to replace T cells for the induction of antibody secretion by human blood lymphoid cells stimulated by pokeweed mitogen (PWM) in vitro. This factor, which will be referred to as RA-SF (synovial fluid), also has the capacity to act as a B cell-stimulatory factor of mouse splenic lymphocytes in the presence of lipopolysaccharide (LPS). Using a test system developed for the definition of interleukin 4 (IL-4), which is a B cell-stimulating lymphokine which preferentially activates the synthesis of selected Ig classes in mouse lymphoid cells, we have shown that RA-SF has properties similar to IL-4 in that it induces differentiation of antibody secretion in the LPS-pretreated mouse cell, but unlike IL-4, which gives IgG1 and IgE, it selectively induces IgG2b synthesis. The present study demonstrates that RA-SF has a biological activity that is reminiscent of other B cell-stimulating mouse lymphokines, but it is biologically distinct from IL-2, IL-4, and IL-5. Recent data also indicate that it is distinct from gamma interferon (IFN-gamma). Therefore, we conclude that the biological activity of RA-SF has properties in common with a T-cell replacing (TRF) and B-cell differentiation factor (BCDF) and probably represents yet another biological activity which so far lacks an experimental counterpart. The relevance of this factor for autoantibody synthesis is discussed.

Animals↗
PubMed1988

Expression of B220 antigen on an interleukin 4- and interleukin 5-producing T-cell line.

The murine T-cell line 2.19, originally used for cloning of interleukin 4 (IL-4) and IL-5, was analysed for surface marker characteristics using monoclonal antibodies and a FACS-4 analyser and found to be positive for the B220 antigen. Thus, this lymphokine-producing cell with characteristic T-cell markers expresses an antigen earlier thought to be specific for B cells. With two-colour fluorescence it was found that a small fraction (2-4%) of Thy 1+ spleen cells from normal CBA mice were also positive for B220.

Animals↗
PubMed1988

Lymphocyte transformation by grass pollen allergens: a study of atopic patients receiving immunotherapy. Part II. Patients during maintenance treatment.

We have previously reported on peripheral blood lymphocyte (PBL) transformation by allergen, PPD as a control antigen and PHA as a mitogen during and after a preseasonal immunotherapy period. The present report describes similar parameters during and after the ensuing maintenance treatment period. Ten patients with grass pollen rhinitis were treated with Allpyral extract and 10 with Conjuvac two-grass mixture. Lymphocyte transformation responses to grass antigen continued to be low for PBL from patients during the maintenance treatment. Postseasonal values were higher during treatment. In late autumn 1980, when treatment had been stopped, there was a spontaneous fall in lymphocyte stimulation values. Occasional high values were noticed in some patients, two of whom had treatment side effects (urticaria). Clinical data during the whole treatment period (skin prick test, provocation tests, serological parameters, total IgE, grass-specific IgE, grass-specific IgG, pollen counts, symptom scores, clinical effect and adverse reactions) have been published separately.

Adult↗
PubMed1988

HLA class II restriction specificity for nickel-reactive T lymphocytes.

Nickel-specific T cells were primed in vitro and restimulated with nickel in combination with autologous or allogeneic antigen-presenting cells. We have previously shown that not only DR, but also DQ molecules may take part in this process. To investigate this phenomenon further we applied recently available knowledge based on studies using specific cDNA probes and Restriction Fragment Length Polymorphism (RFLP), which has revealed a new level of DQ polymorphism, to search for a correlation of this polymorphism in the function of nickel-reactive T lymphocytes. We found that DQ, and presumably also DR, may restrict the proliferative response to nickel. The capacity of various antigen-presenting cells to cause restimulation correlated well, though not completely, with the specificity DQw1. RFLP splits of DQw1 did not yield any additional information on restriction specificity. Experiments using anti DR, DQ and DP monoclonal antibodies were performed, showing similar blocking capacity in all three antibodies. Work with cloned T cells is in progress to obtain more clearcut results concerning the HLA class II restriction of the proliferative T lymphocyte response to nickel.

Antigen-Presenting Cells↗