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Biomedical subjects

M Fischer

Publications and source records attributed to M Fischer.

At least 559 records · Page 31Linked to original sources

[Nuclear medicine methods for the determination of bone mineral content].

Osteoporosis is becoming recognized as a major social and economical health problem. Bone mineral content (BMC) depends on many hormonal and metabolic factors. The pathophysiological mechanism of the loss of bone mass is still unclear. For preventive diagnosis and treatment of osteoporosis, quantitative technology is required that will measure BMC with high precision and reproducibility. Nuclear medical methods permit the BMC of the appendicular skeleton to be measured by single photon absorptiometry. Whole-body BMC, as well as spine and femur BMC, can be measured by dual photon absorptiometry. The results from both procedures are reasonably precise and correlate well with the ash weight of isolated bone. The radiation exposure level in both SPA and DPA is low. SPA and DPA may be used for cost-effective screening of high-risk patients to predict the likelihood of future fractures and control osteoporosis therapy.

Bone and Bones↗

Interferon-gamma is produced by activated immature mouse thymocytes and inhibits the interleukin 4-induced proliferation of immature thymocytes.

We have recently shown that interleukin 4 (IL-4) (formerly called BSF-1) is a potent stimulator of fetal and adult immature thymocyte proliferation and that adult L3T4-/Lyt-2-thymocytes can be stimulated by calcium ionophore (A23187) and phorbol ester to secrete IL-4 (Zlotnik, A., J. Ransom, G. Frank, M. Fischer, and M. Howard. 1987. Proc. Natl. Acad. Sci. (USA) 84:3856). This report shows that fetal thymocytes (day 15 of gestation) can also be activated to produce IL-4 suggesting that IL-4 may be a mediator of fetal as well as adult immature thymocyte proliferation. Furthermore, we demonstrate that interferon-gamma (IFN-gamma) inhibits the IL-4-mediated proliferation of both fetal and adult L3T4-/Lyt-2-thymocytes. The inhibition of proliferation is blocked by anti-IFN-gamma antibody and is unaffected by indomethacin suggesting that IFN-gamma directly inhibits immature thymocyte proliferation. IFN-gamma does not block the IL-4/phorbol myristate acetate-mediated proliferation of an adult thymocyte population, which is enriched for L3T4-/Lyt-2+ and L3T4+/Lyt-2- cells, suggesting that the inhibitory effect of IFN-gamma is limited to the immature thymocyte population. Both fetal (day 15) and adult L3T4-/Lyt-2--thymocytes can be activated to secrete an IFN-gamma like activity. This activity is neutralized by a monoclonal anti-IFN-gamma antibody indicating that the activity is due to IFN-gamma. mRNA analysis of adult L3T4-/Lyt-2- thymocytes stimulated with A23187 and phorbol myristate acetate confirms that mRNA for both IL-4 and IFN-gamma is induced in adult L3T4-/Lyt-2- thymocytes. These results indicate that IL-4 and IFN-gamma can regulate immature thymocyte proliferation.

Animals↗

Lymphokine-mediated induction of antigen-presenting ability in thymic stromal cells.

We have established and characterized long term thymic stromal cultures from BALB/c (H-2d) and CBA/J (H-2k) mice. All cultures contained multiple adherent cell types, whereas some also contained thymic macrophages (TM). Culture supernatants from all cultures tested contained macrophage colony-stimulating factor activity, whereas only cultures with TM had soluble or membrane-associated interleukin (IL)-1. However, a thymic epithelial cell line (3D . 1), cloned from one of these cultures, produced IL-1 bioactivity. Further analysis confirmed the production of IL-1 alpha mRNA by the epithelial cell. No IL-2 or IL-4 (formerly called B cell stimulatory factor 1) activity was detected in any of the cultures. Antigen-presenting (AP) ability was determined using the chicken ovalbumin (OVA)-specific, I-Ad-restricted T cell hybridoma 3DO-18.3. Harvested TM exhibited antigen-specific, Ia-restricted AP ability which was enhanced by IL-4 as well as interferon-gamma (IFN-gamma). In contrast, AP ability was detected in non-macrophage stromal cell cultures (NMSC) only after preincubation with IFN-gamma. AP by preinduced NMSC was also Ia-restricted and could be blocked by anti-I-Ad antibodies. Since the T cell receptor of 3DO-18.3 is known to recognize a peptide produced by CNBr degradation of OVA, these observations suggest that both TM and NMSC can process OVA to produce this peptide. Glutaraldehyde-fixation experiments confirmed that NMSC must process native OVA into antigenic peptides for successful AP. Assays using several cloned stromal cell lines of different lineages suggested that only epithelial cells could be induced with IFN-gamma to exhibit competent AP. Given the possible role for IFN-gamma in the maintenance of Ia in the thymus, we investigated whether IFN-gamma production could be ascribed to a subpopulation of thymocytes. Culture supernatants from calcium ionophore and phorbol ester-stimulated peanut agglutinin-negative, but not peanut agglutinin-positive, thymocytes induced AP ability in NMSC. Thus, some thymocytes can produce an Ia-inducing lymphokine (most likely IFN-gamma) which may play an important role in T cell ontogeny through its effects on both thymic macrophages and thymic epithelial cells.

Animals↗

Evidence for effects of interleukin 4 (B cell stimulatory factor 1) on macrophages: enhancement of antigen presenting ability of bone marrow-derived macrophages.

We have studied the effects of recombinant mouse interleukin 4 (IL 4) (previously known as B cell stimulatory factor 1) on the antigen-presenting ability of murine splenic B cells and bone marrow macrophages. Our assay is based on the induction of antigen-presenting ability in these cells after incubation with IL 4 for 24 hr. The presenting cells were then used to stimulate IL 2 production by antigen-specific, I-Ad-restricted T cell hybridomas, a response mainly dependent on the induction of Ia antigens. Consistent with our previously published data using partially purified natural IL 4, we show here that recombinant IL 4 (but not interferon-gamma (IFN-gamma) or IL 1) induces antigen-presenting ability in B cells. Recombinant IL 4 was also found to induce antigen-presenting ability in a cloned, bone marrow derived-macrophage cell line (14M1.4), and in normal bone marrow-derived macrophages. These macrophage populations also respond to IFN-gamma showing enhanced antigen-presenting ability (mediated by increased Ia antigen expression). A small but significant increase in Ia antigen expression was also detected in 14M1.4 macrophages induced with IL 4. However, additional analysis suggested that the effect of IL 4 on 14M1.4 is different from that of IFN-gamma, because IL 4 (but not IFN-gamma) is able to maintain the viability and increase the size of and metabolic activity of bone marrow macrophages. However, IL 4 may not affect all macrophages because the macrophage cell line P388D1, which responds to IFN-gamma, failed to show enhanced antigen-presenting function after stimulation with IL 4. These observations indicate that IL 4, a lymphokine previously considered to be B cell lineage specific, has effects on macrophages and may be involved in their activation.

Animals↗

Thrombolytic therapy of axillary-subclavian venous thrombosis.

Patients with axillary-subclavian vein thrombosis often have a poor outcome when treated with intravenous heparin sodium and oral warfarin sodium. Four patients were therefore treated with thrombolytic therapy. Good initial and excellent long-term results were achieved. In follow-up that has ranged up to four years, these patients do not have the common complaints of edema, fatigue, cramping, or weakness seen after traditional anticoagulation. Patients have returned to their previous occupations and have normal arm function. Noninvasive Doppler vascular laboratory studies suggest continued patency of axillary veins. Thrombolytic therapy should be considered in the treatment of spontaneous axillary-subclavian vein thrombosis.

Adult↗

Treatment of neuroblastoma with 131I-metaiodobenzylguanidine: experience of the Münster/Kassel Group.

I-131-metaiodobenzylguanidine was used for treatment of neuroblastoma stage IV in three children after surgery and or chemotherapy had failed to be effective. In two of the children with multilocular lesions, after an impressive improvement of clinical symptoms tumor progression was observed. Because in about 25% of children with relapsing neuroblastoma complete remission may be achieved by combining surgery, chemotherapy, and I-131-MIBG treatment, this therapeutic modality should be included in the therapeutic strategy of stage III and IV neuroblastoma.

3-Iodobenzylguanidine↗

[Contamination of foodstuff by gases from tetrachloroethene emissions from a dry cleaners].

Tetrachloroethene (perchloroethylene) and other volatile organic compounds may contaminate the surroundings of dry-cleaning units. Increased concentrations of tetrachloroethene were found in food, human hair, textiles and dust from a vacuum cleaner in a home situated above a dry-cleaning unit. The concentrations were found to be extremely high in food rich in fat. The analytical procedure for the above-mentioned samples is described.

Air Pollutants↗

A three-year prospective study of systemic manifestation in rheumatoid arthritis.

Rheumatoid arthritis (RA) as a systemic disease can attack many other organs in addition to the joints. A variety of pathological lesions of the blood vessels are responsible for the extra-articular features (EAF). In the present study, we investigated firstly whether the presence of blood vessel changes in one organ--namely the skin--may indicate blood vessel pathology and, consequently, EAF in other organs. Secondly, we investigated the number of EAF in individual patients with RA, and observed whether this changed during the course of the disease. Fifty-one RA-patients (40 female, 11 male; ages had a mean of 49.5, minimum 19, maximum 73 years; mean duration of RA was 7.3, minimum 0.25, maximum 41 years) were included in the study. Punch biopsies from the posterior calf were examined immunohistologically for vessel wall immune deposits. Further, EAF were determined by means of instrumental clinical methods such as pulmonary function test, echocardiography, electromyography, and nerve conduction velocity measurement. At the first investigation 21/51 patients had skin vessel wall immune deposits (SVWID). Five patients--all showed SVWID at first investigation--died during the three-year investigation period, 10 patients could not be followed-up for unknown reasons; the skin biopsy of one patient could not be assessed. At the final investigation, we found SVWID in 11/35 patients. SVWID-positive patients had more EAF compared to SVWID-negative patients; this was true both, at the first investigation (1.85 EAF/patient vs 1.05 EAF/patient) and at the final investigation (1.91 EAF/patient vs 0.67 EAF/patient).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Molecular cloning and physical mapping of the genome of insect iridescent virus type 6: further evidence for circular permutation of the viral genome.

A defined and complete gene library of the Chilo iridescent virus (CIV) genome was established. The CIV DNA was cleaved with restriction endonucleases EcoRI, NcoI, SphI, and BamHI or double digested with BamHI/SalI and the resulting DNA fragments were inserted into the corresponding sites of the bacterial vectors pACYC184, pKm2, pL-ES-C3, and pAT153 using T4 DNA ligase. All cloned fragments were identified by digestion of the recombinant plasmids with different restriction enzymes and checked by hybridization of recombinant plasmid to viral DNA. This analysis revealed that sequences representing 100% of the viral genome were cloned into the EcoRI site of pACYC184. Although the CIV genome is linear, all 32 EcoRI fragments have been cloned directly. This suggests that the CIV genome is circularly permuted. In addition, NcoI(72%), SphI(40.7%), BamHI (11.6%), and BamHI/SalI(39.7%) DNA fragments of the viral genome were inserted into the corresponding sites of pKm2, pL-ES-C3, and pAT153, respectively. The physical map of the viral genome was constructed using the established gene library for restriction enzymes ApaI, BamHI, EcoRI, NcoI, SalI, and SmaI. Although the CIV genome is linear, this analysis revealed that the restriction maps of the viral genome are circular. This finding supports the hypothesis that the CIV genome is circularly permuted.

Cloning, Molecular↗

Interaction of Mycoplasma mobile 163K with erythrocytes.

Mycoplasma (M.) mobile 163K isolated from fish was investigated for its hemadsorbing, hemagglutinating, and hemolysing capacities and for its ability to adhere to erythrocytes. Hemadsorption to the colonies of M. mobile occurred with ovine, bovine, equine, trout, and carp erythrocytes and was inhibited by treatment of the mycoplasmas with substances acting on proteins (pronase, trypsin, glutaraldehyde), heat, UV-irradiation and homologous antiserum. Hemadsorption could be prevented also by treatment of the erythrocytes with neuraminidase. In liquid medium ovine erythrocytes were agglutinated and afterwards lysed by M. mobile. The erythrocytes which were adsorbed to the colonies of M. mobile were finally lysed also. Darkfield preparations showed the ability of M. mobile to adhere to erythrocytes and also its hemagglutinating properties.

Animals↗

[Comparative studies of the diagnostic value of various parameters of Doppler frequency spectral analysis of the carotid artery].

Angiographic findings in 94 internal carotid arteries were compared to different parameters of Doppler frequency spectral analysis: systolic and late diastolic peak frequency of the internal carotid artery, ratio of the internal and common carotid systolic and late diastolic peak frequency, spectral broadening as calculated by subtracting internal carotid mean frequency from systolic or late diastolic peak frequency respectively. The normal values were calculated as the 97.5% confidence interval of these parameters in angiographically normal vessels. Specificity, sensitivity, overall accuracy and negative as well as positive predictive value were also calculated. The diagnostic value of the systolic peak frequency of the internal carotid artery proved not to be exceeded by any of the other parameters.

Arterial Occlusive Diseases↗

Interleukin 4 is a growth factor for activated thymocytes: possible role in T-cell ontogeny.

We have shown that recombinant or natural interleukin 4 (IL-4) (formerly called B-cell stimulatory factor 1) induces proliferation of activated adult or fetal thymocytes. In the case of adult thymocytes, IL-4 in combination with Con A or phorbol 12-myristate 13-acetate (PMA) stimulated the proliferation of peanut agglutinin (PNA)-negative (-) thymocytes, while PNA-positive (+) thymocytes showed only marginal responses. Further investigation revealed that day 14-17 fetal thymocytes, purified L3T4- LyT2- double-negative adult thymocytes, and single positive L3T4+ LyT2- or L3T4- LyT2+ thymocytes failed to respond to IL-4 or PMA alone but proliferated strongly with both IL-4 and PMA. In contrast, purified double-positive L3T4+ LyT2+ adult thymocytes showed only a marginal proliferative response to these stimuli. Responsiveness of thymic subpopulations to PMA and IL-4 could be inhibited with anti-IL-4 but not with anti-IL-2 monoclonal antibodies, indicating that they were IL-2 independent. Finally, we have observed that supernatants from calcium ionophore and PMA-stimulated adult double-negative L3T4- LyT2- thymocytes induce proliferation of double-negative adult thymocytes. This latter response is inhibited by anti-IL-4 monoclonal antibodies, suggesting that under appropriate stimulation conditions, these immature thymocytes are able to produce IL-4. These observations suggest a role for IL-4 in T-cell ontogeny.

Animals↗

Generation and characterization of three new monoclonal antibodies detecting the allospecificities HLA-A2,w69, HLA-A3 and HLA-B13.

Immunization of balb/c mice with peripheral blood mononuclear cells of a leukemic patient possessing the antigens HLA-A2,3; B7,35 resulted in the polymorphic monoclonal antibody (moab) UL-101/68 (IgM) defining HLA-A3. Immunization of a second group of balb/c mice with the lymphoblastoid cell line BER homozygous for HLA-A2; B13 revealed two polymorphic moabs UL-39/10 (IgG3) specific for HLA-B13 and UL-39/24 (IgG2b) defining HLA-A2,w69. Immunoprecipitation and polyacrylamide gel electrophoresis with the two moabs of the IgG isotype confirmed the class I structure of the recognized antigens.

Acute Disease↗

The importance of skin vessel wall immune deposits in the course of the systemic and articular features of rheumatoid arthritis. A prospective study.

Fifty-one rheumatoid arthritis patients were examined prospectively during a 3-year investigation period by means of immunohistological, histological, and instrumental clinical methods. Skin vessel wall immune deposits (SVWID) were found in 21/51 patients at the first and in 11/35 patients at the concluding investigation. Patients with SVWID showed more extra-articular features, more rapid progress of joint damage, higher mortality frequency, higher inflammatory activity, and higher levels of circulating immune complexes, compared with patients without SVWID.

Arthritis, Rheumatoid↗