Genetic control of effector cell characteristics: con A-induced suppressor cells carry H-2 I region encoded determinants.
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Biomedical subjects
Publications and source records attributed to E Möller.
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A 51-year-old patient with aplastic anaemia in whom a successful allogeneic bone-marrow transplantation had been performed developed acute graft-versus-host disease in spite of prophylactic administration of methotrexate. There was severe liver injury but no involvement of the skin or intestines. When prednisone therapy was introduced the fever and the eosinophilia disappeared and liver damage was rapidly reversed. There was no haematological impairment. It would seem warranted to consider a wider use of prednisone in the treatment of acute GVHD in human recipients of allogeneic bone-marrow.
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Peripheral blood lymphocytes from nine patients with chronic lymphatic leukaemia (CLL) have been stimulated by photohaemagglutinin, pokeweed mitogen and Epstein-Barr virus. Our results provide proof that the leukaemic B cells in CLL are capable of responding to mitogenic signals by producing and secreting antibodies, transforming into blast cells, and, probably, increasing their rate of DNA synthesis.
By means of a microculture technique and calculation of incorporation of 14C-thymidine, cerebrospinal fluid (CSF) lymphocytes from multiple sclerosis (MS) patients showed low or absent proliferation when stimulated with phytohaemagglutinin, concanavalin A, or pokeweed mitogen, in contrast to peripheral blood lymphocytes (PBL) obtained simultaneously and investigated in parallel. A lower proliferation of CSF lymphocytes compared with PBL was also found in acute aseptic meningitis, although it has been reported that CSF lymphocytes show greater proliferation than PBL when specifically stimulated. The low proliferation of MS CSF lymphocytes on mitogen stimulation may be a consequence of prolonged sensitization to an as yet unidentified antigen. The proliferation of MS CSF lymphocytes was not improved by adding irradiated PBL, making helper cell insufficiency less likely. MS CSF had no inhibitory effect on proliferation of PBL, arguing against an inhibitory effect of soluble factors in the CSF as an explanation for the depressed response of CSF lymphocytes.
HLA genotypes were characterized in a large family of 48 individuals in three generations. In this family, carriers of the proband's disease-predisposing haplotype commonly expressed clinical signs of illness, manifested as psoriasis and/or arthritic lesions. From these data, and from other family studies, presented previously, we have concluded that cutaneous and/or joint lesions may be signs of disease in carriers of the predisposing HLA haplotype. We have investigated HLA-A, B, C and D/DR antigens in the family members. This gave us the opportunity to evaluate the validity of different assays for the determination of HLA-D alleles in a family material where the MLC tests formed the basis for a correct assignment of HLA-D determinants. The HTC method and the PLT assay were both afflicted with specific typing problems, partly due to the existence of cellular cross-reactions between HLA-D determinants, which seemed to be reminiscent of serological DR crossreactions.
The HLA antigens B7 and Dw2 occurred at elevated frequencies in 105 multiple sclerosis (MS) patients (49 and 47%, respectively), compared to healthy controls (29 and 30%), especially in MS patients with oligoclonal CSF-IgG (51 and 50%), in cases with CSF-IgG index values above 1.5 (64 and 64%), and in those with the most malignant course of the disease (47 and 59%). Normal or only slightly elevated frequencies of B7 and Dw2 were found in MS patients without oligoclonal CSF IgG (35 and 29%), normal CSF-IgG index (43 and 39%), and the most benign course (42 and 37%). No correlation was found between the HLA type and measles virus antibody titers in serum or a measles virus antibody response within the CNS.
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339 Evicrol fillings were clinically re-examined 0,52 to 2 years after insertion. The comparison of the results obtained with those from silicate cement fillings (Hildisch) evidenced that the properties of Evicrol are better. In assessing Evicrol for a prolonged period, special attention must be paid to the higher percentage (18--33%) of discolourations appearing already within 1--2 years.
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The activity of 1-[2-(beta-naphthyloxy)ethyl]-3-methyl-2-pyrazolin-5-one (= BAY g 6575) was evaluated in models of experimental thrombosis caused by traumatically induced damage of vessel segments. After prophylactic administration of BAY g 6575 (0.3 mg/kg p.o.) to rats the thrombus formation was significantly reduced in the carotid artery as well as in the jugular vein. The thrombus formation in the femoral arteries of rabbits is inhibited at a minimal effective dose of 1 mg/kg p.o. The incidence of occlusive thrombi is not influenced. BAY g 6575 is 10 times more potent than acetylsalicylic acid (ASA). In the arterial system the thrombus formation is frequently completely abolished.
Renal graft survival was better for the patients receiving blood transfusions or treated with dialysis before transplantation. Graft survival was more strongly correlated with pretransplant dialysis than with blood transfusion.
Purified protein derivative (PPD) of tuberculin was found to induce antibody secretion and DNA synthesis in human lymphocytes from blood, spleen, tonsil and lymph node. Antibody secretion was measured as plaque-forming cells (PFC) against fluorescein isothiocyanate (FITC) coupled sheep red blood cells (SRBC) in a haemolysis-in-gel assay. Peak antibody secretion by 100 micrograms/ml of PPD was usually seen on day 6 for blood lymphocytes, and varied from day 3 to day 6 for spleen cells. Peak DNA synthesis for blood lymphocytes stimulated by various concentrations of PPD ranged from day 4 to day 7. The highest number of PFC in tonsil and spleen cells was induced by PPD compared to Staphylococcus aureus bacteria Cowan 1, lipopolysaccharide (LPS) and pokeweed mitogen (PWM). Antibody secretion by PPD was not affected when phagocytic cells were removed by iron treatment. PPD stimulated a higher DNA synthesis in unseparated lymphocytes or mixtures of T and B cells than in enriched T or B cell suspensions. PPD did not induce PFC in B cells enriched by the removal of sheep erythrocyte rosette-forming cells (E-RFC). However, more PFC were stimulated by PPD in enriched E-RFC compared to unseparated lymphocytes, which may indicate that most of the FITC-SRBC reactive B cells also form rosettes with SRBC.
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A family with hereditary optic atrophy in 4 members of 3 generations is described. The clinical findings differ from those previously observed in hereditary optic atrophy and in Leber's disease, indicating that the hereditary optic atrophy described in this report represents a new disease entity, which is inherited in an autosomal, dominant way with incomplete penetrance. Analyses of the cerebrospinal fluid and serum did not reveal signs of immunoglobulin synthesis within the central nervous system, i.e. findings encountered in a considerable proportion of patients with optic neuritis. An association was found between the family members affected by the disease and the major histocompatibility system haplotype A2 B8. A linkage thus occurred between the disease and the HLA region on human chromosome No. 6.
A monkey antiserum against HLA-A28 was raised by immunization with papain-solubilized antigens. The titre of this serum was 1/370 for beta2-microglobulin (beta2m) 1/750 for A28 and 1/200 for the cross-reacting HLA-A2 determinant. This serum was highly mitogenic for human blood lymphocytes. Mitogenicity was reduced or abolished after absorption of the serum on a beta2m-spharose column. Column-eluted anti-beta2m antibodies were not mitogenic. However, mitogenicity was restored by reconstitution with unabsorbed and absorbed antibodies. Mitogenicity was target cell specific. Tuhs, cells from all individuals were activated by the unabsorbed serum. The absorbed anti-A28 serum was mitogenic only for target cells carrying A28 and/or the cross-reacting determinant A2, but not for cells lacking either of these antigens. A definite gene-dose effect was recorded, since target cells homozygous for A2 responded better to polyclonal activation by the primate serum than cells which were heterozygous.
Neonatally induced fully tolerant mice possess cytotoxic effector cells, specific for the tolerizing antigens, which can be induced by polyclonal T cell activators in vivo (Con A) on in vitro (poly A:U). Therefore, clonal deletion of specific effector cells is eliminated as the mechanism by which skin grafts are retained in tolerized mice.