[Use of blood components, albumin and artificial colloids. The National Hospital 1979-84].
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Biomedical subjects
Publications and source records attributed to B G Solheim.
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The reactivity of monoclonal mouse anti-human antibodies specific for mononuclear cell surface antigens were studied by the indirect immunofluorescence technique in frozen synovial tissue sections from patients with rheumatoid arthritis (RA). Most of the proliferating synovial lining cells were positive for HLA-DR antigens and monocyte-specific antigens, since they reacted with the OKIa1 and OKM1. Cells positive for HLA-DR and monocyte antigens were also seen scattered or in small nests in the synovial stroma, probably representing synovial cells or monocytes/macrophages. Some of the HLA-DR-positive cells may also be B lymphocytes or activated T cells. Endothelial cells were also HLA-DR antigen-positive. Monoclonal antibodies with specificity for all T cells (OKT3), for helper/inducer cells (OKT4), and for suppressor/cytotoxic cells (OKT8) reacted with cells often located in follicle-like structures around vessels. Cells with the T4 phenotype tended to be located in the centre of the follicles, whereas the T8 positive cells were more peripherally situated. In most instances fewer cells were positive for the T8 than for the T4 marker. In some instances there was as many T8-positive cells as T4-positive cells. Complete lack of T-lymphocyte subpopulations was not seen.
The distribution of T-cell subsets has been examined in cell suspensions from lymph node biopsies from 37 non-Hodgkin lymphomas (NHL) of B-cell origin and 8 cases of Hodgkin's disease (HD). T-inducer/helper cells (T4+ cells) and T-suppressor/cytotoxic cells (T8+ cells) were identified by the monoclonal antibodies OKT4 and OKT8, respectively. Compared with reactive lymph nodes the T-cell subset distribution was aberrant in 18/37 (48.6%) of the B-cell lymphomas. The T-suppressor subset was dominating cells in 14/37 (37.8%) and the T-helper subset in 4/37 (10.8%) of the cases examined. In patients with leukaemic disease, a concordant T-cell subset distribution in lymph nodes and PBL was observed in 5 out of 6 cases. HLA-DR antigen was examined in a selected number of cases with a heteroantiserum. In general, the T-cells from neoplastic tissues expressed an increased percentage of HLA-DR antigen. This was most pronounced in cases with a dominance of T8+ cells, in which the majority of T8+ cells expressed HLA-DR antigen. These findings suggest that an increased proportion of activated T-suppressor cells are present in a proportion of B-cell lymphomas. Possible clinical and biological implications are discussed.
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In vitro priming experiments were performed with lymphocytes from members of two different families carrying Dw-,DR2 or Dw2,DR2 haplotypes. It was demonstrated that lymphocytes could be primed to allogeneic HLA-D determinants without detectable priming to the associated HLA-DR determinant, even when the priming cell was also HLA-DR incompatible to the responding cell. It was further shown that the unknown HLA-D determinants of the two families (e.g., Dw-) were different, one of them showing cross-reactivity to Dw2. Priming to MT1 determinants or to Lewis antigens could not be detected.
The outcome of 461 prospectively HLA-A, -B and -C typed and 193 prospectively HLA-DR typed cadaveric kidney transplants in one center was followed. We found a significant beneficial effect on graft survival both of HLA-A and -B as well as of HLA-DR matching between donor and recipient, while no effects of HLA-C compatibility could be detected. The effect of HLA-DR matching was clearly more pronounced than that of HLA-A and -B matching, and a possible influence of matching for HLA-A and -B could only be seen in the HLA-DR mismatched combinations. Pretransplant blood transfusions were associated with an increased graft survival only in patients receiving HLA-DR mismatched transplants. We conclude that major emphasis should be laid on obtaining HLA-DR compatibility in clinical renal transplantation.
Tissue sections of ethanol-fixed, paraffin-embedded specimens from human kidney, placenta and umbilical cord were studied by indirect immunofluorescence with a rabbit antiserum to HLA--DR antigens from B lymphocytes. Capillary walls in the kidney showed specific staining both in glomeruli and around tubuli. Conversely, HLA--DR-like antigens were not detected in the walls of larger vessels, in tubular cells, or in the epithelium of Bowman's capsule. HLA-DR-like antigens of kidney elements thus seemed to be restricted to capillary endothelial cells. In specimens from umbilical cord and placenta, HLA--DR-like antigens were not detected in the walls of capillaries or larger vessels. Isolated endothelial cells from the umbilical vein were likewise negative.
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HLA-DR-like antigens and secretory component (SC) were localized immunohistochemically in adjacent tissue sections of ethanol-fixed paraffin-embedded jejunal mucosa from control subjects and patients with coeliac disease (CD) or dermatitis herpetiformis (DH). HLA-DR-like antigens were found in a patchy distribution apically in the columnar epithelial cells facing the gut lumen and in the upper part of the crypt epithelium. The staining pattern was similar in controls and patients with CD or DH. SC was normally most abundant in the crypt epithelium but the concentration of SC in the surface epithelium increased with increasing villous atrophy both in CD and DH patients. Despite this sign of immaturity, the surface cells retained their capacity to express HLA-DR-like antigens in the pathological mucosa.
To investigate the influence of matching for HLA-DR antigens in renal transplantation, we assessed the outcome of 170 prospectively HLA-typed cadaveric kidney transplantations performed since 1977 in one center. We found a beneficial effect on graft survival of HLA-DR compatibility between donor and recipient (P < 0.05). A possible effect of matching for the HLA-A and B antigens could be seen only in the HLA-DR-mismatched combinations. Pretransplantation blood transfusions were associated with increased graft survival only in patients receiving HLA-DR mismatched transplants (P < 0.02). We conclude that major emphasis should be placed on obtaining HLA-DR compatibility renal transplantation. (N Engl J Med. 1980; 303:850-4).
An allotransplantation of a partly developed premolar from a 12-year-old daughter to her mother is reported. The tooth graft was selected by the use of HLA-A, -B, -C and DR typing and the MLC tests. Follow-up over a 3-year period included periodic identically taken radiographs, electric and galvanic pulp tests and tests for cytotoxic antibodies. Almost complete closure of the apex of the tooth has occurred with no sign of root resorption. The transplant has remained vital, and no production of antibodies against the graft has occurred.
One hundred ninety-one consecutive living related transplants performed from 1969 to the end of 1978 have been analyzed for the effect of pretransplant blood transfusions. Superior graft survival was observed in transfused patients transplanted with a one HLA haplotype-disparate kidney, whereas no effect of blood transfusions could be observed on the survival of HLA-identical transplants. The frequency of first rejection episodes was significantly reduced in transfused compared to nontransfused one haplotype-mismatched transplants, while no influence of blood transfusions was seen in patients with HLA-identical transplants. The survival of patients was, however, not influenced by previous transfusions. Pretransplant hemodialysis improved graft survival and patient survival; the difference was, however, only significant at 2 years in the one haplotype-mismatched group. When analyzed separately, both blood transfusions and hemodialysis had a beneficial effect on graft survival in one haplotype-mismatched transplants.
Sections of ethanol-fixed, paraffin-embedded tissue specimens from different parts of the human gastrointestinal tract were stained by an indirect immunofluorescence method with a rabbit antiserum to HLA-DR-antigens from B lymphocytes. A specific staining reaction was seen in a patchy pattern apically in the columnar cells of the normal small intestine, decreasing in intensity from the top of the villi towards the crypts. No HLA-DR-like antigens could be detected in colon or stomach epithelium, whereas cells with the morphology of lymphocytes and histiocytes in the lamina propria and also capillary walls were specifically stained throughout the gastrointestinal tract.
Three-hundred-and-ninety-five candidates registered for a first cadaveric renal transplant have been analyzed for the effect of pre-graft blood transfusions. Of these, 348 patients were transplanted, 45 died prior to transplantation and two patients have not yet received a transplant. Slightly less than half of the transplanted patients had been transfused, and those received five or more transfusions demonstrated a superior graft survival. This was pronounced in all HLA incompatible transplants who had received five or more transfusions. In patients who received less than five transfusions, only one-two HLA antigen incompatible transplants demonstrated increased graft survival. The frequency of rejection episodes was significantly decreased in all transfused compared to non-transfused groups. Among the patients dying while waiting for a transplant, the majority had been transfused, and a significantly higher proportion of them had cytotoxic HLA antibodies, compared to those who were transplanted.
Prospective HLA-DR typing and B cell cross-match tests were performed in 177 cadaveric transplants using a modified NIH technique, 24 selected HLA-DR typing sera and B cells separated from peripheral blood in recipients and from spleen in donors. Actuarial graft survival after one year was 60% in HLA-DR compatible transplants and 30% and 18% in transplants mis-matched for 1 and 2 HLA-DR antigens. The favorable prognostic influence of HLA-DR compatibility was observed both among HLA-A, -B compatible and incompatible transplants. Sharing of HLA-DR antigen(s) between donor and recipient was also prognostically beneficial. Standard cross-match tests were negative in all transplants. B cell cross-match tests were positive in 17 cases, and one of these transplants was very acutely rejected. Actuarial graft survival after three months was 35% in B cell cross-match positive grafts versus 53% in negative ones.