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Biomedical subjects

S F Goldmann

Publications and source records attributed to S F Goldmann.

At least 73 records · Page 4Linked to original sources

Fourth component of complement (C4) polymorphism in human orthotopic liver transplantation.

C4 polymorphism was investigated in 13 orthotopic liver transplantations. It could be shown that recipient C4 phenotype disappears after transplantation and is replaced by donor phenotype on days 10-19 posttransplantation. This indicates that C4 is mainly produced in the liver. The delayed appearance of donor C4 phenotype compared with other complement components produced in the liver cannot be explained by different rates of synthesis or serum protein levels. The limited number of patients investigated in this study does not permit assessment of the role of C4, C3, Bf, and HLA-A, B, and DR in orthotopic liver transplantation.

Alleles↗

Detection of the genetic polymorphism of human C2 (native protein and C2a fragment) by immunoblotting after polyacrylamide gel isoelectric focusing.

The polymorphism of the second component of human complement (C2) was studied by means of isoelectric focusing in polyacrylamide gels followed by immunoblotting with a specific antihuman C2 antibody. The polymorphism was studied in native C2 and in the C2a fragment obtained by activation of the classical pathway with heat-aggregated human IgG. Serum samples previously typed with the hemolytic overlay technique were analyzed. They comprised samples of homozygous C2*C, C2*B, C2*Q0, heterozygous C2*BC and C2*CQ0 individuals. The patterns obtained by immunoblotting corresponded to those obtained by the hemolytic overlay technique. As expected, the homozygous C2*Q0 sample (complement C2 deficiency) did not show any band pattern. The C2a fragment presented also a polymorphic variation which correlated exactly with the native C2 polymorphism. It appears thus that the polymorphic site of the C2 protein is carried by the C2a fragment for the C2*C and C2*B variants. In addition, this method is easier to perform than the common hemolytic overlay technique and the rare C2-deficient serum is not needed.

Complement C2↗

[Bone marrow transplantation in panmyelopathy, acute leukemia and chronic myelocytic leukemia: results of the Ulm Transplantation Group].

From 1972-1983 53 patients underwent bone marrow transplantation. The median age was 18 years (3-41). 27 patients suffered from severe aplastic anaemia, 22 patients had acute leukaemia and 4 patients had chronic granulocytic leukaemia in chronic phase. Out of 22 patients with acute leukaemia, 2 had florid leukaemia, 2 had an early relapse and 18 patients were in first or second remission of their disease. 2/53 patients received a syngeneic transplant, 51/53 patients an allogeneic transplant. 47/51 patients had a HLA-A, B, C-identical, MLC-negative sibling donor, 1/51 had a HLA-A, B-C-identical, MLC-positive sibling donor, 2/51 a HLA-phaenotypical identical parental donor and 1/51 a HLA-identical, MLC-negative unrelated donor. The comparison of the results obtained in patients with severe aplastic anaemia transplanted from 1972-1979 with those transplanted from 1980-1983 shows that the bone marrow transplantation has to be performed in an early stage of the disease before the patients become multiple transfused, sensitized and severely infected and that the conditioning regimen for polytransfused patients has to be more intensive than in untransfused patients. From the patient group transplanted 1972-1979, only 1/14 patients is a long-term survivor in contrast to 8/13 patients transplanted from 1980-1983. 11/22 patients with acute leukaemia are alive between more than 5 years and 14 days after bone marrow transplantation. Only 1/4 patients, who were transplanted not in remission, is alive.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Immunoreconstitution in severe combined immunodeficiency after transplantation of HLA-haploidentical, T-cell-depleted bone marrow.

Immunological reconstitution by transplantation of HLA-haploidentical, paternal bone marrow was attempted in four infants with severe combined immunodeficiency who lacked HLA-identical donors. To prevent graft-versus-host disease, T lymphocytes were removed from the grafts by agglutination with soybean agglutinin and rosette formation with sheep red blood cells. None of the patients received conditioning treatment before transplantation. Normal, donor-derived cellular immune functions developed in all four patients within several months of transplantation. Threatening complications of graft-versus-host reactions were not seen. All four patients remain in excellent health 12-15 months after discharge home, with persisting normal T-cell functions.

Bone Marrow↗

A patient, mosaic for Rh and Fy antigens lacking other signs of chimerism or chromosomal disorder.

A patient who shows two populations of RBC, differing in their Rh and Fy antigens, was investigated but no other sign of chimerism or mosaicism in a variety of other antigenic systems, including serum and enzyme polymorphisms and HLA antigens, was observed. His karyotype, as investigated on lymphocyte and fibroblast cultures, was normal. Possible explanations of the observed phenomenon are discussed.

Alleles↗

Influence of Lewis and other blood group systems in kidney transplantation.

In 167 first cadaver kidney recipients and their donors the blood groups ABO, Rhesus, Lewis, MN, Ss, P, Kell and Duffy were determined. The influence of incompatibility in each system as well as of simultaneous presence of several mismatches was analysed. Whereas one-year graft survival of Lewis-compatible grafts was 67 per cent (p = 0.02). The other blood groups showed no significant effect on graft outcome. Cumulative red cell incompatibilities, however, led to decreased survival rates. One-year graft survival in the group with greater than or equal to 4 incompatibilities was only 51 per cent versus 69 per cent in transplants with less than 4 incompatibilities (18% difference, p less than 0.01). When the Lewis system was excluded from analysis, the difference in survival rates was reduced to only six per cent. These data indicate that cumulative incompatibilities of red cell antigens have an unfavourable effect on graft survival. Of the different blood groups, the Lewis system is of major importance.

Blood Group Antigens↗

[HLA and bone marrow transplantation (BMT) (author's transl)].

Patient survival after BMT is directly correlated with the HLA-type of the donor. The survival rate after BMT from an HLA-genotypically identical sibling is 56% in acute leukemia, 55% in combined severe immunodeficiency disease (SCID) and 67/83% in severe aplastic anemia patients. The usage of only HLA-D identical related or unrelated donors in SCID revealed a 37% survival, compared to 18% survival in acute leukemia and 11% in severe aplastic anemia using HLA-phenotypical identical or HLA-D identical related donors. BMT from HLA-phenotypical and MLC identical unrelated donors resulted in death of the grafted patients. Non of the patients grafted with HLA-different marrow survived BMT. Survival of BMT patients depended beside the histocompatibility matching on the clinical treatment and the clinical constellation of the patient: The survival rate decreased in aplastic anemia patients due to sensibilisation caused by pre-BMT blood transfusion and was significantly higher in leukemia when BMT was performed in remission.

Acute Disease↗

Limited value of in vitro techniques for the detection of leukocyte alloantibodies during granulocyte transfusion therapy.

A 23-year-old male patient undergoing first induction chemotherapy for acute myeloid leukaemia received granulocyte transfusions on 10 consecutive days. An average of 2.1 X 10(10) granulocytes was given per square metre body surface area per day. Transfusion reactions and absence of post-transfusion granulocyte increment after the fifth granulocyte transfusion suggested the presence of leukocyte antibodies. However, no antibodies were detectable at this time by the lymphocytotoxicity test, the indirect granulocyte immunofluorescence test, or the platelet suspension immunofluorescence test. In contrast to the clinical observation, the serological detection of leukocyte antibodies was only possible 1 day after the last granulocyte transfusion.

Adult↗

Lymphocytotoxic antibodies in patients receiving granulocyte transfusions.

The presence of lymphocytotoxic antibodies was studied in 22 patients receiving granulocyte transfusions. Due to previous blood transfusions 7 out of 22 patients had lymphocytotoxic antibodies before granulocyte transfusions were started. 6 out of 15 unsensitized patients developed antibodies during granulocyte transfusion therapy, and 9 out of 15 patients had no detectable antibodies at any time. Transfusion reactions occurred in the presence of lymphocytotoxic antibodies not directed against donor cells.

Adolescent↗

Rhesus incompatibility and aplastic anemia as the consequence of split chimerism after bone-marrow transplantation for severe combined immunodeficiency.

A patient with severe combined immunodeficiency received three transplants of bone marrow from the HLA-B- and -D-identical mother. The first transplantation led to a severe graft-versus-host reaction followed by immunological reconstitution. A split chimerism was found with engraftment only of the maternal lymphocytes. Five months after the transplantation an autoimmune hemolytic anemia was observed which was due to rhesus incompatibility as well as polyspecific antibodies. At the same time agranulocytosis developed and 9 mth after the first transplantation the child suffered from aplastic anemia. Two further attempts failed to engraft the maternal hematopoiesis. The child died during the treatment with cyclophosphamide as conditioning for a third transplantation.

Agranulocytosis↗

Measurement of cell mediated cytotoxicity by post-labeling surviving target cells.

The 51Cr release assay (CRA) is the commonly accepted technique for measurement of cell mediated cytotoxicity. This assay shows some disadvantages when mononucleated cells of human peripheral blood (MNC) are used as effector and target cells. The uptake of 51Cr by PHA stimulated lymphocytes is low compared to the spontaneous release. In an attempt to develop a cytotoxicity assay suitable for human lymphocytes we used 14C-TdR to label target cells surviving after contact with effector cells. Cytotoxic lymphocytes were generated by incubation of MNC with irradiated allogeneic MNC for 6 days. On day 6 the effector cells are irradiated and co-cultured with PHA stimulated target cells. Twenty-four hours later 14C-TdR is added. After an additional 24 h the cultures are harvested and 14C-TdR taken up by target cells is measured. It is shown that the effector cells are still cytotoxic after irradiation. These cells do not take up 14C-TdR. Cell-free supernatants do not influence the uptake of 14C-TdR by target cells. The results obtained with this assay correlate very well with those obtained by the CRA, if the spontaneous release does not exceed 30%.

Adult↗

Beneficial effect of granulocyte transfusions in patients with defects in granulocyte function and severe infections.

A 3-year-old boy (patient A) with a congenital and a 24-year-old man (patient B) with an acquired granulocyte function defect received supportive granulocyte transfusions for the management of severe infections. The boy had suffered from recurrent infections since bith. His granulocytes showed in vitro almost no chemotactic responsiveness, an impaired phagocytosis and reduced intracellular killing of Candida albicans. Family studies suggested that it was an inherited autosomal recessive defect. The child developed a Pseudomonas pneumonia at the age of 3 years, which did not respond to antibiotic therapy. Granulocyte transfusions were then started and soon after the fever and pneumonia disappeared. Patient B showed the haematological signs of a preleukaemic state. He had 3 recurrent episodes of furunculosis which led each time to cellulitis and septic temperatures accompanied by symptoms of an enterocolitis. Tests of granulocyte function in vitro showed reduced intracellular killing of Staphylococcus aureus. Granulocyte transfusions were started, since no clinical improvement could be attained by antibiotics. With transfusion therapy, fever, cellulitis and enterocolitis disappeared each time.

Adult↗