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Biomedical subjects

E Möller

Publications and source records attributed to E Möller.

At least 163 records · Page 9Linked to original sources

Demonstration of a helper factor(s) with T-cell-replacing activity in synovial fluid.

Cell-free synovial fluid (SF) obtained from patients with rheumatoid arthritis contains a helper factor(s) capable of augmenting the generation of plaque-forming cells (PFC) in pokeweed mitogen (PWM)-stimulated normal peripheral blood mononuclear cells (PBMC). This helper factor behaves like a polyclonal B-cell activator, in that it triggers the formation of IgM, IgG, and IgA PFC. However, SF has little or no effect on the proliferation of PWM-activated PBMC. Furthermore, SF was capable of replacing T cells for PWM-induced differentiation but not proliferation of enriched human blood B lymphocytes. No helper factor or T-cell-replacing activity was found in SF from patients with traumatic synovitis. Fractionation of SF containing helper activity on staphylococcal protein A column indicated that the activity is induced by biologically active molecules distinct from materials that preferentially bind to protein A such as IgG immune complexes. We conclude that the present activity has striking similarities to the recently described B-cell differentiation factor that is produced by specifically activated T-cell lines in vitro.

Arthritis, Rheumatoid↗

Lymphocyte transformation by grass pollen allergens. A study of atopic patients receiving immunotherapy.

Peripheral blood lymphocyte (PBL) transformation by allergens, PPD antigen and PHA mitogen, was followed in 20 allergic patients with grass pollen rhinitis, during and after a preseasonal immunotherapy. Ten patients were treated with Allpyral and 10 with Conjuvac two-grass mixture. Lymphocyte proliferative responses to grass antigens decreased during therapy for most of the patients. Higher values than before treatment were seen in August. Three patients had increased values during the preseasonal treatment. One stopped treatment because of discomfort, the other two got urticaria during the ensuing winter seasons. No effect of immunotherapy was seen on the PPD or PHA response of cells. Cellular changes in relation to changes in specific IgE and IgG antibodies are discussed.

Adult↗

HLA antigens in selective IgA deficiency: distribution in healthy donors and patients with recurrent respiratory tract infections.

HLA-A, B, C and DR typing was performed in healthy IgA deficient donors and in IgA deficient patients with recurrent respiratory tract infections. In healthy donors, a strong association with HLA B8 and DR3 was observed. In the patient group however, no statistically significant association with these antigens could be found. In contrast, an increased frequency of HLA B40 was noted. The preference for HLA B8/DR3 in healthy donors could not be attributed to higher levels of serum immunoglobulins since no major differences in the concentrations of IgM, IgG or the IgG subclasses were seen between the two groups.

Dysgammaglobulinemia↗

No demonstrable association between HLA DR4 and in vitro collagen reactivity as determined by the production of leukocyte inhibition factor.

Eight HLA DR4 positive and 9 HLA DR4 negative healthy volunteers as well as 2 DR4 positive and 1 DR4 negative patients with rheumatoid arthritis (RA) were compared for leukocyte inhibition factor (LIF) production and lymphocyte proliferation in response to native and denatured collagen types II and I/III. Purified protein derivative (PPD) of tuberculin served as a positive control in the LIF assay and PPD and phytohaemagglutinin (PHA) in the lymphocyte proliferation test. No significant difference in responsiveness to collagen was detected between these two HLA groups. The reactivity to collagen was not affected by removal of OKT8+ lymphocytes. The present results are in conflict with earlier reports by Solinger et al. (1981) and Solinger & Stobo (1982). The reason for the discrepancy has not been resolved.

Antibodies, Monoclonal↗

B cell differentiation factor in synovial fluid of patients with rheumatoid arthritis.

In this paper we have summarized our findings on immune activity in patients with Rheumatoid Arthritis. RA is characterized not only by the formation of various autoantibodies but also of a hyperreactivity of the B cell system, shown as an increased DNA synthetic rate of blood non-T, non-monocytic lymphocytes as well as an increased number of actively antibody secreting cells both in the blood and the synovial fluid. Synovial fluid contains biological activity which synergizes with PWM for the induction of Ig-secreting cells in blood from healthy controls. The factor can also substitute for T cells in the PWM-induced antibody synthesis in vitro. This activity fits well with the finding that SF contains a factor which induces increased formation of IgG in LPS-pretreated mouse cell cultures. Experiments show that the factor leads to a preferential increase in the production of IgG2b antibody secreting cells. Therefore, we conclude that synovial fluid contains a B cell differentiating factor with a selective effect on the induction of a particular IgG subclass.

Antibody Formation↗

Response of elevator activity during mastication to treatment of functional disorders.

The pattern of elevator activity during mastication in temporal and masseter muscles of 37 patients with functional disorders and pain in the masticatory system was studied before and after conventional treatment and compared with a control group of 43 subjects. As compared to controls, patients before treatment chewed with greater relative strength (percent of maximal elevator activity), longer relative contraction times (percent of total duration of chewing cycle) and stronger intermediary activity between strokes. These parameters of muscle coordination are proposed as quantitative estimates of "hyperactivity". Conventional treatment abolished pain, tenderness and other symptoms and signs completely in 18 patients in whom the most significant findings in the muscles under study were reductions in absolute and relative contraction times ascribed to increased stability produced by occlusal adjustment. It is suggested that relatively shorter pauses before treatment impaired blood flow and that their prolongation following treatment improved circulation. During the strong, dynamic contractions of mastication, masseter muscles tended to be more susceptible to hyperactivity than the temporal muscles.

Dental Occlusion↗

Follow-up of children of insulin dependent (type I) and gestational diabetic mothers. Growth pattern, glucose tolerance, insulin response, and HLA types.

Fifty-three children of insulin dependent (IDM) and 20 children of gestational diabetic mothers (IGDM) representing 80 and 91%, respectively, of all surviving infants of diabetic mothers born between 1969 and 1972 at Sabbatsberg's hospital, Stockholm, participated in the follow-up study. The first follow-up examination was performed when the children had reached approximately 5 years of age and included measurement of height and weight, insulin response to intravenous glucose, and HLA typing. When the children were approximately 11 years old, a search was performed in the national register for type I diabetes in children in order to ascertain the frequency of type I diabetes mellitus in the total series (n = 88). The majority of children had a normal height for age and desirable weight for height. At the first follow-up all children had normal glucose disappearance rates (kt) and the insulin response including the early insulin response to glucose were not different between IDM and IGDM groups. The frequency distribution of HLA antigens (A, B, C) was not different from normal and there was no association between HLA B 8 and/or B 15 and early insulin response or kt values. At the second follow-up, two children of type I diabetic mothers had acquired type I diabetes, both were HLA B 15 positive, had normal kt values at the first follow-up, one with low, one with a high early insulin response. The frequency of type I diabetes in offspring of insulin dependent diabetic mothers was 3%.

Adolescent↗

In vitro testing for cobalt sensitivity: an aid to diagnosis.

Peripheral blood lymphocytes from 45 patients with a positive patch test to cobalt chloride (CoCl2) and 37 controls were stimulated with various concentrations of CoCl2 and/or cobalt sulphate (CoSO4) or cobalt nitrate (Co(NO3)2) or cobalt acetate [CH3COO)2Co) for various days in culture. Lymphocytes from 35 of these patients showed a significantly greater response than that of the controls. The response occurred in the T enriched population and was monocyte dependent. The strength of the in vivo serial dilution test results did not correlate well with the height of in vitro responses. Lymphocytes from 3 nickel and/or chromium sensitive patients failed to respond to stimulation with cobalt compounds thus confirming the specificity of the reaction. The DNA synthesis test seems to be a reliable in vitro method to aid in the diagnosis of cobalt sensitivity.

Acetates↗

Blood transfusions as pretreatment for kidney transplantation: immunization rate and effect on cellular immune response in vitro.

A group of 28 untransfused uremic patients was given five or more units of stored blood as pretreatment for kidney transplantation; 9 patients formed lymphocytotoxic antibodies against B cells and 1 patient developed multispecific antibodies against both B and T cell panels (greater than 80% reactivity). During the same period 22 previously transfused patients received up to five transfusions as pretreatment for kidney transplantation. B cell antibodies were formed by 10 patients, and 4 of these patients also formed T cell antibodies, 2 with broad reactivity. Cellular immune reactivity in vitro was studied on frozen cells from 17 randomly chosen patients. After five blood transfusions no significant changes were seen in blood lymphocyte responses to phytohemagglutinin (PHA), Concanavalin A (Con A), or in mixed lymphocyte cultures (MLC) and cell-mediated lympholysis (CML). After transfusion 3 patients got Non-A, non-B hepatitis and were withdrawn for up to six months from the transplantation list because of increased S-ALAT and S-ASAT. Of the 50 patients, 27 have received kidney grafts, 6 out of 20 who were sensitized, and 21 out of 30 who were nonsensitized. Because of positive crossmatches no patient with multispecific T cell antibodies has received a graft. We conclude that our transfusion regimen for kidney recipients has rendered barely one-third of the patients sensitized (mostly against B cells) and 3 out of 50 hypersensitized. No effect on T cell reactivity could be seen following five planned transfusions. Because fewer patients with antibodies received grafts (30% with antibodies, as compared with 70% without [P less than 0.01]) the blood transfusions seem to have led to a selection effect.

Antibodies↗

Ventricular arrhythmias and left ventricular dysfunction in familial cardiomyopathy.

In familial cardiomyopathy (CM), different forms of myocardial abnormalities including asymmetric and symmetric hypertrophy and dilated left ventricles are presented, mostly showing varying hereditary penetrance. This study presents a family with CM including three major clinical manifestations: severe ventricular arrhythmias, repolarization abnormalities and left ventricular hypertrophy. This triad was strikingly consistent in the two generations examined. The familial pattern with an autosomal dominant inheritance did not show any linkage to the HLA region.

Adult↗

Spontaneous DNA synthesis in rheumatoid arthritis: evidence of enhanced circulating non-T-cell proliferation.

3H-thymidine incorporation in cultures of peripheral blood mononuclear cells from patients with seropositive rheumatoid arthritis (RA) and healthy controls was measured in vitro in the absence of added stimulants. A significantly higher level of spontaneous DNA synthesis was found in cultures of mononuclear cells from patients with clinically active RA than from patients with inactive disease and normal controls. This activity was more apparent in 24-h cultures than in 72-h cultures. There was no correlation between DNA levels and IgM rheumatoid factor (RF) titres. When T- and non-T-cell populations were separated and cultured simultaneously with unfractionated cells, only non-T cells maintained high levels of DNA synthesis, and enrichment of surface membrane Ig+ (SmIg) cells was generally associated with enhancement of 3H-thymidine incorporation. Furthermore, no difference was found in spontaneous DNA synthesis between cultures either containing or depleted of phagocytic cells. Moreover, the addition of graded numbers of autologous monocytes to highly purified T- and non-T-cell populations did not alter the background DNA synthesis. Thus, endogenously activated cells in RA patients are neither T lymphocytes nor monocytes. A regulatory influence by monocytes could not be demonstrated. It is suggested that cells actively engaged in DNA synthesis in RA blood are non-T cells in origin, most probably B lymphocytes.

Adult↗

Complete heart block--another HLA B27 associated disease manifestation.

An increased prevalence of ankylosing spondylitis and other HLA B27-associated rheumatic diseases has recently been demonstrated in a group of men with permanent pacemaker-treatment. The purpose of the present study was to find out if HLA B27 was associated with severe bradyarrhythmias also in the absence of rheumatic disease. The frequency of B27 was determined in 83 permanently paced men with complete heart block, in whom presence of radiological or clinical signs of a B27-associated rheumatic disease had been excluded. Eighty-four healthy subjects were HLA typed for comparison. HLA B27 was found in 17% of the patients and in 6% of the controls, a significant difference with P = 0.017 (Fisher's exact test). The present study suggests that, in a subgroup of patients with complete heart block, the development of heart block is B27-associated, and that the pathophysiological mechanism is similar to that leading to ankylosing spondylitis. Another B27-associated disease manifestation has been demonstrated.

Adolescent↗

Hereditary ring sideroblastic anaemia and Christmas disease in a Swedish family.

The association of hereditary ring sideroblastic anaemia with Christmas disease in a Swedish family is described. We have studied the transmission of the sideroblastic trait, in relation to HLA groups and Christmas disease, and also evaluated the erythrocyte morphology, uroporphyrinogen-I-synthetase activity and S-ferritin for the detection of latent cases of ring sideroblastic anaemia. The proband had ring sideroblastic anaemia, Christmas disease and haemochromatosis. 3 cases of ring sideroblastic anaemia were found among the 12 family members studied. Using the factor IX deficiency as a marker of the X chromosome, it appeared that autosomal transmission of the sideroblastic trait was most likely. The sideroblastic trait did not seem to be linked to HLA-A3-alloantigen. Erythrocyte morphology was normal in all non-anaemic subjects. S-ferritin was found to be increased in all 3 cases of sideroblastic anaemia as well as in 1 non-anaemic relative. Erythrocyte uroporphyrinogen-I-synthetase was elevated in 10 of the 12 family members; those with sideroblastic anaemia had the highest values indicating that uroporphyrinogen-I-synthetase is of importance in the disturbed haem-synthesis of ring sideroblastic anaemia. This interpretation is supported by the positive correlation between S-ferritin values and the uroporphyrinogen-I-synthetase activity.

Anemia, Sideroblastic↗

Lymphocyte stimulation by trivalent and hexavalent chromium compounds in patients with chromium sensitivity. An aid to diagnosis.

Peripheral blood lymphocytes from 31 patients with a positive patch test to potassium dichromate (K2Cr2O7) and from 24 healthy controls were stimulated with various concentrations of chromium chloride (CrCl3) and/or chromium basic sulphate (Cr4(SO4)5(OH)2), sodium chromate (Na2CrO4) or K2Cr2O7 on various days of culture. Both trivalent and hexavalent chromium compounds could induce lymphocyte transformation, as measured by increased DNA synthesis. The response occurred in the T-enriched population and was monocyte dependent. Lymphocytes from 11 of these patients could not be stimulated with the chromium compounds in vitro, whereas the in vivo serial dilution test (SDT) was positive in 4 and negative in 7 of them. Lymphocytes from 2 patients with a negative in vivo SDT showed a positive response in vitro. The strength of the in vivo SDT results did not correlate well with the height of in vitro responses. The DNA synthesis test seems to be a reliable in vitro method to aid in the diagnosis of chromium sensitivity.

Adult↗

Markedly elevated serum IgE levels following allogeneic and syngeneic bone marrow transplantation.

Serum IgE levels were studied in 25 bone marrow transplant recipients (in 12 patients twice weekly and in 13 patients, at random). A 2-748-fold increase in serum IgE was recorded in 20 of the 25 patients after transplantation, the highest IgE value observed being 8,000 kU/liter. The IgE elevation appeared concomitantly with acute graft-versus-host disease (GVHD) in 14 patients. Both events occurred on day 24 +/- 2 (mean +/- SE). When the acute GVHD was diagnosed, there was a significant increase in serum IgE as compared to the first posttransplantation value. In one patient in whom GVHD recurred, a second IgE peak was seen, and in another patient with flaring GVHD, IgE levels increased on several occasions. In 6 patients without clinical signs of GVHD, a rise in IgE occurred on day 35 +/- 12. One of these patients was grafted with marrow from her identical twin. The rise in IgE did not correlate with an elevated proportion of eosinophil granulocytes. In the majority of the patients, no correspondent increases in serum IgG, IgA, or IgM were seen during the period with increased IgE after transplantation.

Adolescent↗

[Sacroiliitis].

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Arthritis↗

Experience with a cooperative bone marrow transplantation program in Stockholm.

Twenty-seven patients (age range from 1 to 55 years) were included in a cooperative bone marrow transplantation program in Stockholm. Of eight patients with severe aplastic anemia (SAA), two died following graft rejection and six (75%) are alive between 3 months and 4 1/2 years after transplantation. Two patients with end stage leukemia died of septicemia and bleeding shortly after transplantation. Thirteen of 17 patients (76%) with acute leukemia in their first or second remission are alive 1 to 16 months after transplantation. Death was caused by septicemia in two patients, interstitial Candida pneumonitis in one and gastrointestinal bleeding in association with graft-versus-host disease in one. Among the leukemic patients all deaths occurred in subjects over 17 years of age and all 10 children are alive. No relapse has yet been seen. Successful bone marrow transplantations were carried out utilizing ordinary hospital resources only. This justifies the practice of performing transplantations in subjects with SAA and acute leukemia in remission even outside specially equipped and designed bone marrow transplantation units.

Acute Disease↗