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Biomedical subjects

M Fricke

Publications and source records attributed to M Fricke.

At least 19 recordsLinked to original sources

High efficiency beam splitter for multifocal multiphoton microscopy.

In this article we present the development of a multibeam two-photon laser scanning microscope. A new type of beam splitter to create the multitude of laser beams is described. This type of beam splitter has higher transmission and generates more uniform beams than can be achieved with the microlens approach used by other groups. No crosstalk exists between the different foci due to small temporal delays between the individual beams. The importance of dispersion compensation to obtain maximum efficiency of the microscope is discussed. With optimum compensation the fluorescence signal was raised by a factor of 14. Different modes of detecting the fluorescence signals and their effect on imaging speed and resolution are discussed.

Animals↗

Rheumatoid factors in systemic lupus erythematosus: association with clinical and laboratory parameters. SLE study group.

The prevalence and clinical and laboratory associations of IgM, IgG and IgA rheumatoid factors (RF) were determined in 352 patients with systemic lupus erythematosus (SLE). IgM, IgG, and IgA class RF were detected in 17.9%, 20.5%, and 20.5% of the sera, respectively. RF were associated with sicca syndrome, hypergammaglobulinemia, high titer of antinuclear antibodies, anemia, SSA- and SSB-antibodies, and with the presence of HLA-DR3. RF correlated negatively with nephritis and livedo racemosa. Moreover, we observed an association of RF and parameters of inflammatory activity such as elevated erythrocyte sedimentation rate (ESR) and leukopenia. Analysis of immunoglobulin classes revealed that laboratory parameters of inflammatory activity, SSA- and SSB-antibodies and HLA-DR3 correlated with IgA RF only. IgA RF define a subgroup of SLE patients characterized by distinct autoimmune phenomena and high disease activity in the absence of nephritis.

Antibodies, Antinuclear↗

Thrombomodulin in systemic lupus erythematosus: association with clinical and laboratory parameters.

Thrombomodulin is an endothelial cell membrane glycoprotein and is detected in plasma and serum after endothelial injury. In our study comprising 311 patients with systemic lupus erythematosus (SLE) clinical and laboratory associations of elevated thrombomodulin serum concentrations were examined. Elevated thrombomodulin concentrations were detected in 7.1% of the SLE patients and were associated with nephritis including the laboratory parameters proteinuria and erythrocyte casts, vasculitis and neurological involvement of the central nervous system. These correlations remained significant after consideration of the influence of renal function. In SLE, the serum thrombomodulin concentration may become a marker to monitor damage of endothelial cells and involvement of the central nervous system.

Enzyme-Linked Immunosorbent Assay↗

Association of IgA anti-dsDNA antibodies with vasculitis and disease activity in systemic lupus erythematosus. SLE Study Group.

Previously it has been suggested that the presence of antibodies against dsDNA of the IgA class may define a subset of systemic lupus erythematosus (SLE) patients suffering from nephritis and arthritis. Therefore, these autoantibodies were measured in sera of 352 patients with SLE, 81 blood donors, and 189 patients with rheumatoid arthritis using a new ELISA based on human recombinant dsDNA as antigen. IgA anti-dsDNA antibodies were found in 19.9% of the sera from patients with SLE, but in none of the sera from 81 normal controls and 189 patients with rheumatoid arthritis. The association of these autoantibodies with 31 clinical and 36 laboratory parameters was calculated. IgA anti-dsDNA antibodies were found to be associated with parameters of disease activity such as elevated erythrocyte sedimentation rate and consumption of complement component C3, and the clinical parameters vasculitis, with necrosis and erythema, but not with nephritis and arthritis. Therefore, IgA anti-dsDNA antibodies define a subset of SLE patients, and monitoring of IgA anti-dsDNA antibodies may be helpful as a prognostic parameter in patients with SLE.

Antibodies, Antinuclear↗

IgM anti-dsDNA antibodies in systemic lupus erythematosus: negative association with nephritis. SLE Study Group.

Antibodies against dsDNA of the IgM class were measured in sera of 352 patients with systemic lupus erythematosus, 81 blood donors and 189 patients with rheumatoid arthritis using a new ELISA based on human recombinant dsDNA as antigen. IgM anti-dsDNA antibodies were found in 52.3% of the sera from patients with systemic lupus erythematosus, but in none of the sera from 81 normal controls and 189 patients with rheumatoid arthritis. The association of these autoantibodies with 31 clinical and 37 laboratory parameters was calculated. There was a highly significant negative correlation between IgM anti-dsDNA antibodies and nephritis as well as all the laboratory parameters indicating renal disease (elevated serum creatinine concentration, proteinuria, erythrocyte casts in the urine). IgM anti-dsDNA antibodies indicate protection of lupus patients against the development of lupus nephritis. Further experiments will show whether application of IgM anti-dsDNA antibodies is effective in treating lupus nephritis.

Antibodies, Antinuclear↗

Self-determination: the panacea for Canadian aboriginal people with disabilities?

Equal access and participation issues are at the forefront of the current disability advocacy movement. Disabled people worldwide are demanding a change in attitudes and policies reflecting their inherent right as citizens to full participation in society. The inequalities faced by the Canadian Aboriginal community with disabilities are magnified by unique socioeconomic, political, environmental, and cultural barriers. The current rate of disability in the Canadian Aboriginal population (31%) is double the national rate. The existing system available to Aboriginal people with special needs has often resulted in an unaccountable and ineffective web of service delivery. This paper documents various aspects of the existing structure of service delivery and the potential barriers to independent living for adults with disabilities living in remote First Nations communities in Northern Manitoba, Canada. Possible advantages and drawbacks to service provision in health transfer from the federal government to First Nation control are explored.

Activities of Daily Living↗

Genetic differences in immune reactivity to mercuric chloride (HgCl2): immunosuppression of H-2d mice is mediated by interferon-gamma (IFN-gamma).

Upon treatment with HgCl2, H-2s mice, such as B10.S, develop an activation of B lymphocytes that depends, at least partially, on activation of T helper type 2 (Th2) cells and results in increased serum levels of IgG1 and IgE, appearance of IgG autoantibodies, and development of immune glomerulonephritis and vasculitis. Results of previous studies and of experiments presented here indicate that the B cell activation and systemic autoimmune disease fail to develop in MHC-congenic B10.D2 (H-2d) and B10.BR (H-2k) mice treated with HgCl2, although B10.D2 T cells showed signs of activation by and specificity for HgCl2 comparable to those seen in strain B10.S. Here, we report that following HgCl2 injections the antibody response to sheep erythrocytes is normal in B10.S, but suppressed in B10.D2 mice. This suppression was prevented by MoAb to mouse IFN-gamma. Conversely, treatment of B10.D2 mice with murine recombinant IFN-gamma (rIFN-gamma) was able to reproduce the immunosuppression seen after HgCl2 treatment. In B10.S mice, it took administration of both rIFN-gamma and HgCl2 to suppress the anti-sheep erythrocyte response. Although rIFN-gamma diminished the increase in IgE serum levels of HgCl2-treated B10.S mice, it failed to prevent their autoantibody production and immune glomerulonephritis. These findings further strengthen the concept that B10.S mice react to HgCl2 by preferential activation of their Th2 cells producing IL-4, whereas B10.D2 mice react to HgCl2 by preferential activation of their Th1 cells, which produce IFN-gamma and thus suppress antibody responses.

Animals↗

Psychophysiological reactivity of borderline hypertensives and their recovery after mental stress.

UNLABELLED: The question of psychophysiological reactivity of borderline hypertensives is still controversial. METHODS: Young males with borderline blood pressure levels and normotensive controls were recruited during a routine examination. Samples of study I comprised 19 subjects, samples of study II 18 subjects. Two stressors were presented (distressing movie, mental arithmetic), each followed by a recovery phase. Systolic and diastolic blood pressure, heart rate, and electrodermal parameters were assessed repeatedly. RESULTS: Borderline hypertensives showed greater reactions to stressors in systolic blood pressure only. Changes in percentage of baseline levels were essentially the same. Recovery after stress did not differ between groups. CONCLUSION: Only moderate support is given to the hypothesis that borderline hypertensives show increased and slowly recovering psychophysiological responses.

Adaptation, Physiological↗

Significance of antibodies to cardiolipin in unselected patients with systemic lupus erythematosus: clinical and laboratory associations. The SLE Study Group.

In a multicentre study anticardiolipin antibodies of the IgG and IgM isotypes were measured by a solid phase enzyme immunoassay in 368 patients with systemic lupus erythematosus (SLE) who were not selected on the basis of features of antiphospholipid syndrome. Clinical and laboratory associations of increased levels of anticardiolipin antibodies were evaluated. IgG and IgM antibodies to cardiolipin were documented in 224 (60.9%) and 128 (34.8%) patients, respectively. Regarding the symptoms of antiphospholipid syndrome, elevated amounts of anticardiolipin IgG were significantly associated with spontaneous abortion (P < 0.001), thrombocytopenia (P < 0.01), livedo reticularis (P < 0.01) and a positive direct Coombs test (P < 0.05), but not with thrombosis or central nervous system diseases such as epilepsy and psychosis. IgM antibodies to cardiolipin were associated with a positive direct Coombs test (P < 0.01), but with no other symptom of antiphospholipid syndrome. The predictive values of anticardiolipin antibody determinations in unselected SLE patients were poor for all features of antiphospholipid syndrome because of high proportions of false-positive and false-negative results. As for other manifestations of SLE, positive correlations between raised antibodies to double-stranded DNA and the occurrence of anticardiolipin antibodies of the IgG isotype were observed, and anticardiolipin IgM was negatively associated with nephritis.

Adolescent↗

Autoantibodies against eukaryotic protein L7 in patients suffering from systemic lupus erythematosus and progressive systemic sclerosis: frequency and correlation with clinical, serological and genetic parameters. The SLE Study Group.

Recent studies have shown that sera of patients suffering from systemic autoimmune diseases contain autoantibodies directed against the eukaryotic ribosomal protein L7 [1]. In the present study we screened a large panel of sera from patients with systemic lupus erythematosus (SLE) for the presence of anti-L7 autoantibodies and their relationship to clinical, serological and genetic parameters of SLE. By means of an ELISA employing recombinant protein L7 as antigen we detected anti-L7 autoantobodies in 172 of 506 SLE sera (34%). Negative correlations were observed between the presence of anti-L7 autoantibodies, serum IgG levels and proteinuria; a potentially positive relationship existed with lung fibrosis. In order to analyse further this possibility we screened sera of 129 patients suffering from progressive systemic sclerosis (PSS) for anti-L7 reactivity; 45 of these patients had lung fibrosis. Of the PSS patients, 41% exhibited anti-L7 autoantibodies, but positive reactions were evenly distributed among patients with and without lung fibrosis. Protein L7 thus represents a major autoantigen of systemic autoimmune diseases, but does not so far define a distinct subpopulation of patients.

Autoantibodies↗

MHC associations of autoantibodies against recombinant Ro and La proteins in systemic lupus erythematosus. Results of a multicenter study. SLE Study Group.

Antibodies against recombinant 52 kD-Ro, recombinant 60 kD-Ro and recombinant La protein were determined by ELISA in over 300 central European patients with systemic lupus erythematosus (SLE). A strong association with HLA-DR3 was found for antibodies against 52 kD-Ro and La, but not for recombinant 60 kD-Ro antibodies in the absence of antibodies against 52 kD-Ro or La. Ro/La negative SLE patients still showed an increased frequency of HLA-DR3 as compared to healthy controls. These results indicated that the preferential formation of Ro and La antibodies was not due to an unspecific stimulatory effect of HLA-DR3 but that the antibody response to certain defined proteins (52 kD-Ro and La) was influenced by MHC genes in SLE. Furthermore, the association of SLE with HLA-DR3 was independent of the effects of DR3 on the formation of 52 kD-Ro and La antibodies.

Antibody Specificity↗

Expanded macrophage precursor populations in BXSB mice: possible reason for the increasing monocytosis in male mice.

The BXSB mouse spontaneously develops an autoimmune disease that resembles human systemic lupus erythematosus (SLE). During their lifetime, male BXSB mice show an increasing monocytosis in the peripheral blood as opposed to their female littermates. This monocytosis is unique among autoimmune-prone mice. To test the hypothesis that alterations at the stem cell level may be responsible for this monocytosis, myeloid bone marrow precursor cells were examined in both male and female BXSB mice from 4 to 40 weeks of age. The number of M-CSF responding stem cells (CFU-M) and the number of GM-CSF responding stem cells (CFU-GM) were higher than in all other inbred mouse strains tested. In addition, male BXSB mice developed a progressive increase of CFU-M and CFU-GM in the bone marrow during their lifetime, which paralleled the peripheral blood monocytosis. The monocytosis in male BXSB mice is the result of a further expansion of the strain-specific high number of macrophage precursors by intrinsic factors, which may be attributed to the influence of the Yaa factor. The sex-specific expanded mononuclear phagocyte system may promote the autoimmune process and may be one reason for the dramatic course of murine SLE in male BXSB mice.

Animals↗

Major histocompatibility complex haplotypes and complement C4 alleles in systemic lupus erythematosus. Results of a multicenter study.

In a multicenter study more than 300 central European systemic lupus erythematosus (SLE) patients were examined for HLA-B, HLA-DR, and complement C4 phenotypes. For 174 SLE patients MHC haplotypes were determined by family segregation analysis, and for 155 patients C4 gene deletions were determined by TaqI restriction fragment length polymorphism. Two haplotypes, B8-C4AQ0-C4B1-DR3 and B7-C4A3-C4B1-DR2, were identified as risk factors for SLE. These findings were confirmed by applying the haplotype frequency difference (HFD) method, which uses nontransmitted haplotypes from the family study as internal controls. Furthermore, only HLA-DR2, but not DR3, B7, or B8, was significantly increased in SLE patients independently of the two risk haplotypes. C4A gene deletions, but not silent C4AQ0 alleles, were increased in SLE patients and neither C4BQ0 alleles nor C4B gene deletions were increased. The observed frequencies of homozygosity and heterozygosity for the two haplotypes and the frequencies of homozygotes for C4AQ0 and C4A deletions did not differ from the expected values, indicating that the risk for SLE is conveyed by single allele effects. In conclusion, there are two MHC-linked susceptibility factors for Caucasian SLE patients carried by the haplotypes B7-DR2 and B8-DR3. The results argue against C4Q0 alleles being the decisive factors increasing susceptibility to SLE.

Alleles↗

Circulating immune complexes in malignant diseases increased detection rate by simultaneous use of three assay methods.

By using three different assay methods, circulating immune complexes have been detected in 85% of sera from patients with malignant melanoma, and in 77% of sera from patients with breast cancer. These methods were a C1q-binding assay, a double-antibody conglutinin-binding ELISA, and a polyethylene glycol 6000 precipitation technique followed by quantitative determination of immunoglobulins in the redissolved precipitate. Detection rates of circulating immune complexes using any one of these methods separately ranged from 33% to 56%, indicating the presence of different types of circulating immune complexes in cancer patients' sera. The combined use of the three methods mentioned resulted in an increased diagnostic sensitivity and a doubling of the predictive value. However, tests for circulating immune complexes cannot be considered as useful parameters for early diagnosis of cancer, since the comparatively low incidence of malignancies in the population at large, together with the presence of circulating immune complexes in other, nonmalignant, diseases of considerable prevalence, appears to preclude effective application of any nonspecific method for early diagnosis of cancer in general.

Antigen-Antibody Complex↗

Idiotype-bearing peripheral blood lymphocytes in human multiple myeloma and Waldenström's macroglobulinaemia.

Antisera raised against idiotypic determinants (ID) of myeloma proteins and macroglobulins have been used to differentiate peripheral blood lymphocyte (PBL) populations from individual patients. ID-positive lymphocytes not resembling plasma cells have been regularly found in peripheral blood in these diseases. For further characterization ID-positive lymphocytes were enriched from the peripheral blood by affinity chromatography using heterologous anti-idiotypic sera. Two patients with IgG myeloma, one patient with Waldenström's macroglobulinaemia and two persons with benign monoclonal hyperglobulinaemia (BMH) were examined by this technique. The ID-positive PBL population was shown to be heterogeneous with respect to non-tumour-specific surface markers, such as sheep erythrocytes (SRBC), Fc and C receptors. Tumour-specific idiotypic determinants will thus allow a more correct recognition of the total tumour cell compartment in these diseases.

Adult↗

[Prospective studies on the pathologic mechanism of post-spinal headache in a select group of patients (author's transl)].

In this prospective study 613 patients on whom a total of 783 spinal anaesthetics had been performed, all for urological operations, were questioned and examined. Subjective complaints occured in 102 cases (13%) and were found to be more frequent amongst the female patients. 23 cases (2.9%) developed a typical post-spinal headache, this being more likely to occur if the patient was a woman, was young, and if a 22-Gauge needle was used. The headache usually began on getting up on the day of operation or the first post-operative day, and rarely lasted longer than four days. The pathophysiological changes indicate that the headache is caused by a fall in CSF pressure. The therapy and various methods of preventing this complication are discussed, and the other potential neurological symptoms and signs mentioned.

Adult↗