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Biomedical subjects

C Müller

Publications and source records attributed to C Müller.

At least 685 records · Page 38Linked to original sources

The new HLA-DRw6- and 8- associated HLA-Dw HAG specificity defined by homozygous typing cell 9W 1802. Analysis with primed lymphocyte typing clones.

Intrafamilial primary mixed lymphocyte culture (MLC) typing established that an HLA-A, B, C homozygous, DP heterozygous donor HAG was homozygous for HLA-Dw and behaved as a homozygous typing cell (HTC). Both haplotypes of the HTC were HLA-DR identical, but could not be assigned a clear DR specificity, giving reactions with sera containing antibodies against DRw6, DRw8 and TA10. MLC checkerboard studies failed to assign the HTC HAG specificity to any established or provisional cluster, suggesting that it defined a new Dw specificity. Primed lymphocyte typing (PLT) clones derived from intra-familial priming against either HAG haplotype displayed heterogeneous reactivity patterns. One clone was restimulated only by family members and unrelated donors positive for Dw HAG. Other clones were restimulated by determinants associated with either Dw8 or Dw6. Blocking of stimulation with monoclonal antibodies against different class II molecules suggested that while stimulatory determinants associated with Dw HAG and Dw8 were classifiable as HLA-D related, those associated with Dw6 were of a DP-like nature.

Antibodies, Monoclonal↗

Divergent patterns of leucocyte locomotion in experimental post-traumatic osteomyelitis.

Leucocyte locomotion (LL) was evaluated in guinea-pigs with experimental post-traumatic osteomyelitis. Surgical procedure (fracture of the right femur), the number of micro-organisms applied to the fractured site and the time sequence of investigations were kept constant. After the right femur of guinea-pigs had been fractured, the animals were divided into three groups: in group I the fractured site remained uninfected, while in groups 2 and 3 the fractured sites were infected with either Escherichia coli (10(5] or with Staphylococcus aureus (10(4]. In a fourth group, guinea-pigs were anaesthesized only, without any further trauma. LL was significantly depressed in all three groups following trauma on postoperative day 5 as compared to pre-operative levels (P less than 0.01), but had remained normal in guinea-pigs which had been anaesthesized only. While LL returned to pre-operative levels and stayed normal in uninfected guinea-pigs and those which had been infected with E. coli, LL levels fell significantly (P less than 0.05) in guinea-pigs which had been infected with Staph. aureus on postoperative day 55 and remained depressed throughout the observation period of 90 days. These findings emphasize that defects in LL are connected with the infectious agent and are not merely secondary to the process in the osseous tissue.

Anesthesia↗

[Diagnosis of syncopes in suspected arrhythmias].

Several mechanisms lead to attacks with unsuspected sudden and intermittent loss of consciousness. A major cause for such syncopes are arrhythmias. Only in rare cases it is possible to register an ECG during a typical attack despite many newer methods as long-term ECG (LT-ECG), exercise stress test and electrophysiologic investigations. LT-ECG does not record the ECG only during symptomatic periods (syncopes, dizziness, palpitations etc), but also registers asymptomatic AR, which can be precursors of SY. Carotid sinus massage is a valuable tool for the detection of a cardio-inhibitory Carotid-Sinus-Syndrome, which can be treated with PM-implantation. Exercise stress testing induces ventricular arrhythmias, which also indicates AR as underlying cause for SY. Using the invasive electrophysiologic investigation methods the importance measuring supraventricular parameters (SNRT, SA-, AH-interval) or parameters of the AV-nodal conduction (AH-, HV-interval) decreased in contrast to the ventricular stimulation techniques. With these invasive procedures ventricular tachycardias, ventricular flutter or fibrillation can be induced in selected patients, which indicates also a possible arrhythmogenic substrate for SY. In a suspected arrhythmogenic genesis of SY it has to be recommended to perform LT-ECG, carotid sinus massage, exercise stress testing and -- in selected patients -- electrophysiological investigations in addition to the routine-ECG to exclude or confirm arrhythmias as possible substrate for SY.

Arrhythmias, Cardiac↗

[Refusal of catamnestic testing].

From a study of catamnesis involving 866 persons admitted to hospital for psychiatric care (Enquête de Lausanne, Ciompi--Müller), the authors have examined the patients who refused this test, that is to say 10%, trying to determine the characteristics. In comparing the two groups they came to the conclusion that there were no significant differences between them, and that the overall results of the statistic research would not have been modified had the above mentioned persons been included. They therefore recommend discretion, as well as the respect of the individual by not forcing the person to look backwards. They suggest that all studies of catamnesis be conducted by the doctor who treated the patient beforehand, if this is at all possible.

Follow-Up Studies↗

[What does the Doppler ultrasonic technic accomplish in angiology?].

Doppler ultrasound was the most important diagnostic improvement in angiology during the last twenty years. This technique has been used answering the following clinical questions: severity of peripheral vascular disease; diagnostic of cerebro-vascular disease and diagnostic of deep vein thrombosis. Doppler ultrasound provides a clinical useful and objective evaluation of peripheral artery disease. Mönckeberg's sclerosis and leg oedema give false results only. The sensitivity of carotid Doppler investigations is over 90%. Deep vein thrombosis of the leg and pelvis can be diagnosed correctly in about 90% of cases. Ultrasonic methods are not only reliable but have also the advantages of being non-invasive, repeatable and inexpensive.

Arterial Occlusive Diseases↗

Characterisation of renal antigens on distinct parts of the human nephron by monoclonal antibodies.

Ten monoclonal antibodies (TN 1-TN 10) directed against different renal antigens of distinct sites of the human nephron were derived from a fusion between P3-NS1/1-Ag4-1 mouse myeloma and spleen cells of a mouse hyperimmunized against isolated human kidney cells. Two of these reagents (TN 1, TN 10) were shown by immunoperoxidase labelling on frozen sections of five normal kidneys and of other selected human organs, as well as by immunofluorescence studies on normal peripheral blood cells and selected lymphohematopoietic cell lines, to detect antigens exclusively expressed on visceral glomerular or proximal tubular epithelial cells. The other eight antibodies were found to react with different determinants shared between renal structures, muscle cells, different epithelia, B-lymphocytes and granulocytes. In heterogeneous cultures of isolated kidney cells these monoclonal reagents could be used to identify distinct cell types of tubular origin. Thus such hybridoma-derived antibodies provide new tools to correlate structural characteristics of various renal epithelial cells with their functional properties and will contribute to the study of their influence on immunologically mediated kidney injuries in different forms of glomerulonephritis in man.

Animals↗

Myasthenia gravis: overlap with 'polyendocrine' autoimmunity.

81 patients with spontaneously acquired myasthenia gravis (MG) were investigated for the presence of autoimmune (AI) diseases and their sera were tested for a range of organ-specific autoantibodies. 77 of the patients were HLA-phenotyped. Antibody titres to acetylcholine receptors (AChR) were higher in non-thymomatous patients who possessed HLA-B8 (p less than 0.05) and/or -DR3 (p less than 0.05) as compared to patients lacking these HLA antigens. 3 out of 20 (15%) patients with ocular MG, 7/23 (30%) with generalized MG of early onset, 11/23 (48%) generalized MG of late onset and 5/14 (35%) patients with thymoma had either overt AI diseases or significant titres of organ-specific autoantibodies suggesting subclinical AI disease. In ocular MG, low titres and an infrequent finding of antibodies to AChR (32%) as well as the low prevalence of associated autoantibodies and AI diseases indicate that this subgroup of MG consists of patients with restricted AI reactivity. HLA-B8 and -DR3 were present in all the patients with associated AI disorders in the young onset group but in none of the patients with old age of onset. In the young group, 6 out of 7 patients with associated AI conditions were women whereas the sex ratio was about equal in the older cases in both, patients with and without associated AI diseases or autoantibodies. We conclude from these observations that ageing provides conditions that allow the breakdown of self tolerance. The simultaneous presence of HLA B8, DR3 and female sex provide important additional factors for early expression of MG.

Adult↗

HLA-DR-MT matching improves graft survival rate in cadaver kidney transplantation. A prospective multicenter analysis of the South German Cooperative Study Group for Kidney Transplantation.

The influence of prospective HLA-DR matching on the graft survival rate was investigated in a multicenter analysis of 85 transplants. Simultaneously in a retrospective analysis of graft outcome the importance of matching for MT-antigens MT1, MT2 and MT3 as a newly defined B-cell alloantigen system was evaluated. HLA-DR antigens and MT-specificities were determined on B-cells enriched by nylon-wool filtration using locally well characterised HLA-DR antisera and the antiserum set of the 8th International Histocompatibility Workshop ("disease set") which allowed the definition of the HLA-DR specificities HLA-DR 1-9 and of the MT-antigens MT1-3. HLA-DR matching showed a significantly improved graft outcome only in HLA-DR identical donor-recipient combinations. In 11 of 60 patients with one HLA-DR compatibility additional matching for two MT-antigens, however, improved the two year graft survival rate from 60% to 91%. Altogether 17 patients were matched for two MT-specificities with their kidney donor and showed a superior prognosis of 94% at two years compared to 53% or 17% of recipients with one or zero MT compatibility. Graft outcome in this patient group was also superior to that of HLA-DR identical or HLA-AB identical grafts. These data suggested that the MT-system rather than the HLA-DR antigens may be of critical importance in cadaver kidney transplantation. In addition a favorable influence of pretransplant blood transfusions on less HLA-DR matched grafts was confirmed.

B-Lymphocytes↗

Quantitative and qualitative differences in the distribution of HLA class I antigenic determinants in the human thymic compartments.

The topographical distribution of HLA class I antigens has been investigated by the immunoperoxidase technique on normal frozen thymic tissue sections with a panel of mono- and polymorphic monoclonal anti-HLA antibodies. HLA class I framework determinants detected by the monoclonal antibody W6/32.HL were present on 80-90% of cortical thymocytes, as well as on all cortical epithelial and medullary cells. However the staining intensity of cortical thymocytes with this reagent was about threefold weaker than that of the medullary thymocytes. Labelling patterns of selected monoclonal antibodies against matching HLA-A/B allospecificities revealed striking variations in the quantitative expression of certain HLA-A vs. HLA-B locus alloantigenic determinants on cortical thymocytes compared to a consistent staining on almost all medullary cells.

Antibodies↗

A cytotoxic monoclonal antibody specific for the private alloantigenic determinant of the HLA-B 13 molecule.

A murine monoclonal antibody (TU 110) prepared against blast cells of a patient with acute "undifferentiated" leukemia was tested in the microcytotoxicity assay on peripheral blood lymphocytes of 122 normal Caucasian donors. The TU 110 reactivity was found to show a correlation coefficient of 1.0 in population analysis for the presence of the HLA-B locus specificity B 13 as defined by alloantisera. Family segregation studies confirmed MHC linked inheritance of the TU 110 antigenic determinant strictly on HLA-B 13 positive haplotypes. As the first monoclonal reagent against the private specificity of this HLA-B locus antigen, TU 110 provides the possibility to study the structural relationships of sub- and supertypic determinants on this allotype and may help to correlate antigenic domains of HLA-B 13 with definable functional properties.

Animals↗

A cytotoxic monoclonal IgM antibody (Tü 101) directed against an antigenic determinant shared between the HLA-A allospecificities A2 and A28.

A complement-fixing murine monoclonal IgM antibody (TU 101) strictly directed against a supertypic determinant present on the HLA-A locus antigens A2 and A28 was defined from a fusion experiment employing T cell blasts as immunizing cells. The specificity of this antibody was established in the microcytotoxicity assay on 91 normal Caucasian blood donors, as well as in the SpA-Ig assay on a panel of lympho- and hematopoietic cell lines. TU 101 segregates only with its defined HLA allotypes in families. This reagent may be of particular value as a probe for analyzing a molecular relationship of different antigenic determinants on the HLA-A2 and A28 specificities in comparison with two recently defined anti-HLA-A2/A28 monoclonal antibodies and may help to characterize structural variations of these HLA-molecules on a serological and immunochemical basis.

Animals↗