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Biomedical subjects

C A Müller

Publications and source records attributed to C A Müller.

At least 109 records · Page 6Linked to original sources
PubMed1992

Human cytomegalovirus in rejected kidney grafts; detection by polymerase chain reaction.

Human cytomegalovirus (CMV) infections are frequently associated with graft rejection in the immunosuppressed patients following organ transplantation. Thirty-four tissue samples from rejected kidneys and 18 samples from normal adult kidneys obtained from autopsies were investigated for the presence of CMV-DNA by the polymerase chain reaction (PCR) and by immunohistochemistry. DNA extracted from renal tissues after proteinase K digestion was specifically amplified in 32 cycles using primers which flank a 147 bp DNA fragment of the immediate early CMV gene and analysed by slot-blot hybridization with digoxigenin-labelled detection oligonucleotides. CMV-DNA was detected by PCR in a range from 0.1 fg up to 100 fg in 14 (41%) rejected kidney transplants. Comparative immunohistological analysis revealed presence of CMV in only three biopsies of these rejected kidneys. Furthermore, CMV-DNA was also found in four of 18 (22%) normal donor kidneys. These results reveal that CMV is often present in rejected kidneys and that the infection can be transferred from the donor to the recipient, since the normal adult kidney appears to be a frequent site of latency for CMV. No differences in local immunological changes, characterized by interstitial mononuclear leukocyte infiltration as well as by aberrant expression of HLA-class II antigens and of ICAM1 on proximal tubular epithelial cells, could be detected by further immunohistological analysis between grafted kidneys at late stage of rejection with and without CMV infection.

Adolescent↗
PubMed1992

Data modeling for immunological and clinical data of leukemia and myasthenia patients.

In this study it was investigated whether and to what extent semantic data models and their methods for data modeling are useful for adequate representation and integration of immunological and clinical data. To that end the special research program in leukemia research and immunogenetics (SFB 120) of the University of Tübingen was taken as an example. Based on the semantic data model RM/T we propose the design of a database system, report on its realization, and discuss this approach. Using a semantic data model, the quality of data increased considerably. This means, for instance, that the integration of the molecular-biological knowledge allows a better control of the person-related results. Hence, the decisions based of these data may have greater validity and the treatment on leukemia patients can be improved. Furthermore, the elucidation of immune mechanisms concerning auto-immune diseases could be improved.

Autoimmune Diseases↗
PubMed1991

Polymerase chain reaction to evaluate antiviral therapy for cytomegalovirus disease.

A sensitive and specific method to monitor suppression of cytomegalovirus (CMV) replication is essential in patients treated with ganciclovir after allogeneic bone-marrow transplantation. In this study, antiviral therapy of eighteen episodes of symptomatic CMV infection in 15 such patients were followed up clinically and by virus culture and polymerase chain reaction (PCR). Clinical improvement, culture, and PCR were assessed for their ability to predict the efficacy of ganciclovir therapy in each patient. In eleven successfully treated episodes of CMV disease (disappearance of symptoms and improvement in biochemical variables) clinical improvement was associated with an effective suppression of virus replication as shown by negative culture and PCR assays of blood and urine specimens obtained after antiviral therapy. 1 patient who did not improve clinically when receiving antiviral therapy remained both culture positive and PCR positive for CMV. 6 patients with early relapse of CMV disease or who died after an initial clinical improvement were PCR positive but culture negative after termination of therapy. Demonstration of CMV in blood and urine by PCR after stopping antiviral therapy (even when culture is negative) points to incomplete suppression of virus replication. The findings show that PCR is a better predictor of the efficacy of antiviral therapy than are culture or clinical assessment.

Adult↗
PubMed1991

Early occurrence of human cytomegalovirus infection after bone marrow transplantation as demonstrated by the polymerase chain reaction technique.

Twenty-eight patients undergoing bone marrow transplantation (BMT) were followed-up at weekly intervals from day -10 to discharge from hospital after BMT for human cytomegalovirus (HCMV) infection using polymerase chain reaction (PCR), slot-blot hybridization, and conventional virus culture. High specificity of the PCR assay applied could be shown by failure to amplify DNA extracted from a wide range of other viruses frequently infecting marrow transplant recipients. The PCR technique allowed us to diagnose viremia and viruria in 20 (83%) of 24 seropositive patients after BMT, whereas culture assays showed 16 (67%) of 24 of these patients to be viruric and 9 (37%) of 24 cases to be viremic. Slot-blot hybridization showed a frequency of viruria and viremia in 12 (50%) of 24 seropositive patients. By application of PCR techniques, HCMV detection could be achieved even in the very early posttransplant period. HCMV was detected in five patients even before the onset of clinical symptoms of acute graft-versus-host disease. Analysis by PCR techniques of 33 organ biopsy specimens from patients after BMT showed the presence of HCMV in 13 of 14 liver samples obtained from patients with HCMV viremia; three liver specimens from patients without viremia were negative by all the techniques applied. HCMV could also be demonstrated in postmortem lung biopsy specimens from all patients (n = 10) with interstitial pneumonia.

Bone Marrow Transplantation↗
PubMed1991

In vivo induction of HLA molecules in patients with myeloproliferative syndrome during IFN alpha treatment.

Eighteen patients with myeloproliferative syndrome (14 with chronic myeloid leukemia, four with essential thrombocytosis) were investigated for modulation of HLA antigens on peripheral blood lymphocytes, monocytes, and hematopoietic precursors during IFN alpha therapy as a sign of potentially increased immune recognition of malignant cells. After 1 month of IFN alpha therapy, an increased number of monocytes and hematopoietic precursor cells, but not of lymphocytes, expressed HLA-DQ antigens. In addition, a strong induction of HLA class-I antigens was found on both hematopoietic progenitors and normal peripheral blood mononuclear cells. With daily injections of IFN in the first month of therapy stimulation continuously increased, suggested a major effect of IFN alpha on hematopoietic progenitors with sustained enhanced expression of HLA class-I antigens during differentiation of myelomonocytic cells. HLA class-I antigen expression was consistently augmented by IFN alpha in all patients, irrespective of their hematological response.

Blood Cell Count↗
PubMed1991

The pathogenesis of chronic renal failure in diabetic nephropathy. Investigation of 488 cases of diabetic glomerulosclerosis.

Investigation of renal biopsy specimens from 488 patients with diabetic glomerulosclerosis (DGS) of varying severity revealed the following: 1) The severity of DGS increases with the duration of the diabetes. 2) As the severity of DGS increases, it is complicated with increasing frequency by exudative changes, which correspond in detail to hyperperfusion lesions described in the literature. 3) As the severity of DGS increases, the severity of arteriolosclerosis and the incidence of nephrotic syndrome increase significantly. 4) The 5- and 10-year renal survival rates are highest for those diabetic patients in whom the tubules and renal cortical interstitium are of normal appearance. These survival rates are diminished if any of the following are present at the time of biopsy: a) interstitial fibrosis; b) hyperperfusion lesions; c) nephrotic syndrome; d) elevation of the serum creatinine concentration to more than 1.3 mg%. 5) No significant correlation was found between renal survival rate and age, sex, or type of diabetes. 6) The inflammation of the renal interstitium seen in diabetes does not differ from that seen in chronic glomerulonephritis. Monocytes, macrophages, T lymphocytes, fibroblasts and fibrocytes play the major role in this inflammation. This inflammatory process is considered to represent not pyelonephritis, but rather an auto-immune process. In other words, it is proposed that the diabetic kidney fails not only as a result of non-specific glomerular lesions (hyperperfusion lesions) but also because of non-specific tubulointerstitial changes, whereas diabetic glomerulosclerosis alone does not lead to chronic renal failure.

Adult↗
PubMed1991

Mononuclear leukocytes, expression of HLA class II antigens and intercellular adhesion molecule 1 in focal segmental glomerulosclerosis.

Immunophenotyping of infiltrating glomerular and interstitial mononuclear leukocytes performed in renal tissues of 15 patients with focal segmental glomerulosclerosis (FSGS) was compared to 15 normal kidneys in order to investigate a possible role for cell-mediated immunity (CMI) in FSGS. In addition, distribution of HLA class II (-DQ, -DR, -DP and -DY) antigens and of the intercellular adhesion molecule 1 (ICAM-1) as well as the expression of well-defined renal antigens along the human nephron was analyzed. In comparison to normal kidneys, a reduction in HLA class II antigens of ICAM-1 and of renal antigens defined by the monoclonal antibodies TN8-TN10 was observed in sclerotic glomeruli. Furthermore, an increased number of T lymphocytes was found in glomeruli of FSGS with slight predominance of the CD8+ subset. Interstitial inflammation was present in all FSGS cases except 1 with T lymphocytes and monocytes/macrophages constituting the predominant infiltrating cell types. In contrast to the glomerular T cells, the number of interstitial CD4+ cells was greater than the number of CD8+ cells in almost all cases. As a sign of activation, most interstitial inflammatory cells carried HLA class II antigens and some of them also expressed ICAM-1. Proximal tubular epithelial cells often presented an abnormal expression of HLA-DQ and HLA-DP antigens associated with aberrant expression of ICAM-1 and TN8. The number of interstitial mononuclear leukocytes was correlated to serum creatinine levels at the time of renal biopsy. The present results provide further support for the involvement of CMI in the pathogenesis of FSGS.

Adult↗
PubMed1991

Intercellular adhesion molecule-1 expression in human kidneys with glomerulonephritis.

Intercellular adhesion molecule-1 (ICAM-1) plays an important role in immune responses. Expression of this molecule was examined on cryostat sections of 15 normal human and 112 glomerulonephritic kidneys using a specific monoclonal antibody and the indirect immunoperoxidase staining technique. The expression of ICAM-1 on renal structures was compared to that of HLA-DQ, -DR, -DR/DP and -DP antigens. On normal kidneys ICAM-1 was observed on some Bowman's capsular cells and on single glomerular cells which probably represent endothelial and mesangial cells. ICAM-1 was present on peritubular capillaries and on vascular endothelium of large vessels as well as on fibroblasts, whereas no expression of ICAM-1 on proximal tubular epithelial cells (PTECs) was detected. In normal renal tissues the distribution of ICAM-1 was similar to that of HLA-DQ and -DP antigens. In kidneys with different forms of glomerulonephritis especially in association with interstitial inflammation, an abnormal expression of ICAM-1 on PTECs was frequently correlated with aberrant expression of HLA-DQ and -DP antigens. These results further support the hypothesis that PTECs may participate in cell-mediated immune reactions in glomerulonephritis.

Antibodies, Monoclonal↗
PubMed1991

The product of the proto-oncogene c-kit (P145c-kit) is a human bone marrow surface antigen of hemopoietic precursor cells which is expressed on a subset of acute non-lymphoblastic leukemic cells.

A monoclonal antibody (17F11) was raised by immunization of a Balb/c mouse with leukemic blasts from a patient with acute non-lymphocytic leukemia (ANLL). This antibody recognizes most leukemic blasts of myeloid but not of lymphoid lineage and no peripheral blood cells. By screening NIH-3T3 fibroblasts transfected with the human proto-oncogene c-kit (NIH-3T3/hckit) it could be shown that 17F11 specifically recognizes the gene product P145c-kit. Immunofluorescence analysis on normal hemopoietic cells revealed that 17F11 weakly stains 1-3% of bone marrow mononuclear cells (BMMNC). By FACS sorting and colony assays it could be shown that granulocyte--macrophage progenitor cells could be enriched 10-20-fold, granulocyte progenitors 50-80-fold, and erythroid and multipotential progenitor cells 15-20-fold, in the 17F11 positive fraction. Double fluorescence analysis revealed that P145c-kit is co-expressed on 40-60% of the CD34 positive BMMNC. Finally, these data show that P145c-kit is expressed on blast cells from most patients with ANLL (26/30) and chronic myeloid leukemia in blast crisis (7/9), but is absent on blasts from patients with acute lymphoblastic leukemia expressing the T-, B-lineage, or common ALL phenotypes.

Animals↗
PubMed1991

Endoglin is expressed on a subpopulation of immature erythroid cells of normal human bone marrow.

A monoclonal antibody (1G2) was raised by immunization of a Balb/c mouse with the leukemic blasts from a patient suffering from chronic myelogenous leukemia blast crisis (CML-BC). Sequential immunoprecipitation of the protein from human umbilical vein endothelial cells with 1G2 and the endoglin-specific monoclonal antibody 44G4 indicated that both antibodies react with the same molecule, a homodimer of molecular mass 180,000. This protein was first identified on acute lymphoblastic leukemia and was shown to be primarily associated with endothelial cells. In addition, 1G2 and 44G4 identified the same subpopulation of human bone marrow mononuclear cells (BMMNC), as established by two colour immunofluorescence analysis. By cell sorting and colony assays it could be demonstrated that endoglin is not expressed on hemopoietic precursor cells (CFU-G, CFU-GM, CFU-GEMM, BFU-E). May-Grünwald-Giemsa staining of sorted BMMNC revealed that 1G2 recognized immature proerythroblasts and double-fluorescence analysis showed that endoglin is present on a subset of glycophorin A-positive BMMNC. 1G2 was not reactive on bone marrow B-cells (CD19, CD20), T-cells (CD3, CD7), natural killer cells (CD56), myeloid cells (CD13, CD14, CD15, CD33), and on CD34-positive cells. Endoglin contains an arginine-glycine-aspartic acid sequence, a feature generally associated with extracellular matrix proteins which interact with integrins. It is suggested that proerythroblasts may utilize endoglin to interact with integrins in cell-cell adhesion events in the stromal or hemopoietic compartment of the bone marrow.

Animals↗
PubMed1990

[Highly malignant non-Hodgkin's lymphoma in hyper-IgE syndrome].

A largely symptom-free swelling of the right submandibular lymph nodes developed in a 23-year-old woman with hyper-IgE syndrome who had suffered from recurrent staphylococcal abscesses since childhood. Histological examination of the lymph nodes revealed highly malignant non-Hodgkin lymphoma of centroblastic type. Extensive staging tests did not reveal any further tumour manifestations. Because granulocyte chemotaxis is abnormal in hyper-IgE syndrome and the patient also had an infection of an old lung cyst, treatment was restricted to local radiotherapy of the cervical lymph nodes. Since 12 months there has been no recurrence. There is probably no connection between the hyper-IgE syndrome and the development of a malignant non-Hodgkin lymphoma, judging by the results of immunological and immunoelectrophoretic findings.

Adult↗
PubMed1990

Differential regulation of HLA class I genes by interferon.

Allele-specific differences in the regulation of HLA class I genes by type I interferon (IFN) were observed after transfection of eight HLA-B, -A, or -C genes into mouse L cells. HLA-B7 and -Bw64 gene expression was significantly more inducible by type I IFN than the genes coding for HLA-B27, HLA-B51, HLA-B38, HLA-B39, HLA-Cw3, and HLA-A2 antigens. Modification of the 5' end of HLA-B7 and HLA-B27 genes revealed the presence of enhancer sequences responding to IFN treatment in the 5' untranslated region of HLA-B7, but not of HLA-B27 and suggested further, independently acting enhancer elements downstream of the transcription initiation site. Comparison of 5' enhancer region sequences in correlation with type I IFN inducibility of the different HLA class I alleles indicated that the exchange of only two nucleotides in the interferon response sequence (IRS) or enhancer A region of HLA-B7 or -Bw64 could account for nonregulated promoters in all other HLA-A, -B, or -C alleles analyzed. Thus, type I IFN stimulation of HLA class I genes in mouse L cells appears to predominantly operate in most alleles by a mechanism targeted to enhancer sequences downstream of the gene's transcription initiation site.

Alleles↗
PubMed1990

Comparison of different techniques for detection of cytomegalovirus infection following bone marrow transplantation.

A total of 317 different clinical samples obtained from patients following bone marrow transplantation and 56 blood and urine samples from seronegative control persons were screened for the presence of human cytomegalovirus (CMV) using virus culture and slot-blot hybridization. Immunohistochemical techniques using monoclonal antibodies to various viral antigens and in situ hybridization techniques were also utilised for detection of CMV in tissue samples. In cell suspensions of blood, bone marrow and effusions, and in liver biopsies, CMV DNA could be demonstrated more often by slot-blot and in situ hybridization techniques than by virus culture or immunostaining of viral antigens. For detection of CMV in lung biopsies and other clinical samples containing mainly cell-free virus, such as urine, bronchial lavage and throat washings, virus culture was found to be at least as sensitive as the hybridization techniques. Immunostaining proved to be a fast and sensitive technique for detection of CMV in tissues and may thus provide additional information about viral replication and clinical relevance of the virus infection.

Bone Marrow↗
PubMed1990

Association of glomerular and interstitial mononuclear leukocytes with different forms of glomerulonephritis.

Immunophenotyping of mononuclear leukocytes was performed in renal tissue obtained from 69 patients with different forms of glomerulonephritis (GN) and from ten donors' kidneys for transplantation used as controls. A panel of monoclonal antibodies was used in the immunoperoxidase technique on frozen sections to define B- and T-lymphocyte subpopulations, NK cells and monocytes/macrophages, as well as the expression of HLA class II antigens-DQ, -DR and -DP. Quantification of labelled leukocytes revealed a significant increase of CD4+ and CD8+ T-cells in glomeruli of rapidly progressive glomerulonephritis, membranoproliferative glomerulonephritis and even of focal gomerulosclerosis. The number of glomerular monocytes/macrophages was significantly increased only in rapidly progressive glomerulonephritis, whereas in membranoproliferative glomerulonephritis it was decreased. No differences to normal tissue were detected in glomeruli for all other types of inflammatory cells. Interstitial cells were mostly T-lymphocytes in all forms of glomerulonephritis. In all groups the CD4+/CD8+ ratio was somewhat greater than 1 and even about 2 in rapidly progressive glomerulonephritis. Only in particular case was this ratio inversed. High expression of HLA class II antigens was observed on interstitial mononuclear leukocytes, as a sign of their activation. The excess of HLA-DQ-positive cells over the sum of CD14+ and CD20+ cells provides evidence not only for presence of activated T-lymphocytes but perhaps also for accumulation of renal dendritic cells in the interstitium in glomerulonephritis associated with interstitial infiltration.

Antibodies, Monoclonal↗
PubMed1989

Genetic and serological heterogeneity of the supertypic HLA-B locus specificities Bw4 and Bw6.

Gene cloning and sequencing of the HLA-B locus split antigens B38 (B16.1) and B39 (B16.2) allowed localization of their subtypic as well as their public specificities HLA-Bw4 or -Bw6 to the alpha-helical region of the alpha 1 domain flanked by the amino acid positions 74-83. Comparison of their amino acid sequences with those of other HLA-B-locus alleles established HLA-Bw6 to be distinguished by Ser at residue 77 and Asn at residue 80. In contrast, HLA-Bw4 is characterized by at least seven different patterns of amino acid exchanges at positions 77 and 80-83. Reactivity patterns of Bw4- or Bw6-specific monoclonal antibodies reveal two alloantigenic epitopes contributing to the HLA-Bw4 or -Bw6 specificity residing next to the region of highest diversity of the alpha 1 domain.

Amino Acid Sequence↗