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Biomedical subjects

R Arndt

Publications and source records attributed to R Arndt.

At least 91 records · Page 5Linked to original sources

Treatment of NZB/NZW mice with total lymphoid irradiation: long-lasting suppression of disease without generalized immune suppression.

We used total lymphoid irradiation (TLI; total dose = 3400 rad) to treat the lupus-like renal disease of 6-mo-old female NZB/NZW mice. Similar to our past studies, this treatment resulted in a marked prolongation of survival, decrease in proteinuria, and decrease in serum anti-DNA antibodies compared with untreated littermate controls. Although there was no evidence of disease recurrence in TLI-treated mice until after 12 mo of age, the in vitro proliferative response to phytohemagglutinin by NZB/NZW spleen cells recovered within 6 wk such that responses were greater than control NZB/NZW animals. A similar recovery and overshoot after TLI were evident in the primary antibody response to the T cell-dependent antigen sheep red blood cells (SRBC). Both the total and IgG anti-SRBC antibody responses after TLI were greater than those of untreated NZB/NZW controls, and were comparable with those of untreated non-autoimmune mice. Despite this increased response to mitogens and antigens after TLI, we noted a decrease in spontaneous splenic IgG-secreting cells and a decrease in IgG but not IgM antinuclear antibody production. Nonspecific suppressor cells of the mixed leukocyte response were detectable in the spleens of NZB/NZW mice early after TLI. However, the disappearance of suppressor cells was not associated with recrudescence of disease activity. Furthermore, transfer of large numbers of spleen cells from TLI-treated NZB/NZW mice did not result in disease suppression in untreated age-matched recipients. In summary, treatment of NZB/NZW mice with TLI results in a prolonged remission in autoimmune disease, which is achieved in the absence of generalized immunosuppression.

Animals↗

Biochemical characterization of the T-cell alloantigen RT-6.2.

This study presents the partial molecular characterization of the alloantigenic rat T-cell marker RT-6. In contrast to most lymphocyte surface membrane proteins, RT-6 proved to be resistant to short-term (15 min) solubilization by TX-100 at 4 degrees, but could be efficiently solubilized by long-term (16 hr) exposure at 4 degrees or short-term (15 min) exposure at 37 degrees. SDS-PAGE analyses of RT-6.2 immunoprecipitates under non-reducing conditions revealed two bands with apparent molecular weights of 21,000 and 24,000 (25,000 and 28,000 under reducing conditions). Radiolabelled sugars failed to be incorporated metabolically into RT-6.2, neither endoglycosidase-F and 0-glycanase digestion nor NaOH treatment caused any detectable decrease in the molecular weight of RT-6.2, and RT-6.2 failed to bind to any of a series of agarose-coupled lectins with a wide of sugar-binding specificities. These observations suggest that RT-6.2 may lack carbohydrate moieties.

Animals↗

[Changes in immunologic parameters following heart operations with special reference to the postcardiotomy syndrome].

In 29 patients (twelve female, 17 male) the following immunologic parameters were examined before and between days 1 to 3, 6 to 8, 13 to 15 and 20 to 22 after open-heart surgery: T-lymphocytes; immunoglobulins IgG, IgM, IgA, IgE; complement factors C3, C4 and the autoantibodies (Anti-DNA, myocardial antibodies, SMA, ANA, AMA) to assess changes in these parameters and their relationship to postoperative complications, in particular post-cardiotomy-syndrome (PCS). PCS was found in five patients (17.2%), in three fully developed, in two in a partial form. In the very early (first to third day) postoperative course, significant suppression of most parameters was found, most likely due to tissue traumatization intraoperatively as well as to the extracorporeal circulation. There was suppression of T-lymphocytes, immunoglobulins IgG, IgM and IgA and the complement factors C3 and C4. The IgE rose slightly. The serum IgM level appears to be of prognostic relevance since the patients with IgM suppression had a higher incidence of postoperative complications (PCS, pancreatitis). In the later postoperative course IgM, C3 and C4 significantly exceeded the preoperative values. The rise in IgM can be explained as an immunologic answer to a subclinical infection or to an immunization by autoantigenic tissue. The rise in C3 and C4 was interpreted as an acute phase reaction. These changes, however, had no influence on the postoperative course of the autoantibodies, only subsarcolemmal myocardial antibodies were found preoperatively; in four of the five patients with PCS, these myocardial antibodies were present prior to surgery. Postoperative myocardial antibodies were found in 75% of the patients. In all probability they are only indicative of nonspecific myocardial lesions.

Adult↗

Human transitional cell carcinoma in the NMRI-nu/nu mouse bladder: a new animal model for the in vivo use of monoclonal antibodies and cytotoxic agents.

Human transitional cell carcinoma of the bladder was successfully transplanted into the bladder of the NMRI-nu/nu mouse. Transplantation of a single-cell suspension from a human Grade II transitional cell carcinoma had an acceptance rate of 33%. The tumors showed invasive growth and could be identified by an anti-human monoclonal antibody. This tumor model can be valuable as an in vivo test system for the local use of cytotoxic agents and monoclonal antibodies in diagnosis of and therapy for human bladder carcinoma.

Animals↗

Elimination of trinitrophenol-specific antibody response by antigen-toxin conjugates.

The aim of the experiments presented here is the selective inhibition of an antigen-specific immune response. Antigen receptors are used as targets for conjugates of antigens and toxin to eliminate antigen-reactive cells. The trinitrophenol (TNP)-specific immune response can be specifically abrogated by incubating the TNP-keyhole limpet haemocyanin (KLH)-primed spleen cells with TNP-ricin or TNP-chicken IgG-ricin conjugates before in vitro stimulation with TNP-KLH. The rate of elimination is dose-dependent and related to the degree of TNP moieties bound to the toxin molecule. The specificity of the toxin conjugates is demonstrated by treating sheep erythrocyte-primed spleen cells with TNP-IgG-ricin conjugates. These results may have therapeutic relevance for treating autoimmune diseases.

Animals↗

Monoclonal antibody defines CA 19-9 in pancreatic juices and sera.

In a retrospective study pancreatic juice samples (n = 213) and corresponding serum samples (n = 110) were assayed for their concentration of monoclonal antibody defined CA 19-9/GICA (gastrointestinal cancer associated antigen). Serum CA 19-9 values were found to be good diagnostic and discriminating markers for pancreatic disorders and were raised (greater than 50 u/ml) in more than 80% of the pancreatic cancer patients compared to 8.5% of the pancreatitis group and none of the control group. In contrast pancreatic juice CA 19-9 values showed a considerable overlap between groups. On the basis of recent molecular data on the monoclonal antibody 19-9 defined antigen(s)--that is, monosialoganglioside, mucin--it is proposed that the discrepancies between serum and pancreatic juice findings are due to a specific undirected endocrine release of the mucin into sera in pancreatic tumour patients while in pancreatic juices of all diagnostic groups high CA 19-9 activities are either owing to coexistence of glycolipid and mucin or that the latter is a physiologically exocrine product.

Antibodies, Monoclonal↗

Monoclonal antibody-defined human pancreatic cancer-associated antigens.

Three pancreatic cancer-associated antigens were characterized by use of monoclonal antibodies in immunobinding studies with various cellular and soluble target antigens, in immunoprecipitation, and in immunoperoxidase staining. C54-0 represents a tumor-associated Mr 122,000 antigen, which appears to be widely distributed on various epithelial tumors and to a lower extent on normal tissue. C1-N3 antigen exhibited a more restricted distribution, reacting with pancreatic and various gastrointestinal tract tumors as well as with chronically inflamed pancreatic tissue. The most specific antigen expression was observed for C1-P83 antigen, found on all exocrine tumors of the pancreas, but not on normal or chronically inflamed pancreatic tissue.

Animals↗

Influence of cations on the mode of action of miconazole on yeast cells.

The influence of the antifungal agent miconazole nitrate on yeast plasma membranes was studied in a concentration range 0-100 microM. The reaction of 100 microM miconazole with the plasma membranes lead to a rapid breakdown of the transmembrane pH gradient and to an efflux of metabolites from the cytoplasm of the cells. This effect of miconazole could be reversed by mono-, di- and most effectively by trivalent cations due to the formation of miconazole-cation complexes. At a ratio of trivalent cation/miconazole (1:3) the effect was completely reversed. X-Ray diffraction studies indicated a crystalline structure of the aluminium-miconazole complex.

Aluminum↗

[Demonstration of C3-binding circulating immune complexes using Raji, conglutinin and anti-C3 assays--a critical review].

There remains no doubt at the present time, that the appearance of circulating immune complexes in illness accompanying vasculitis and for glomerulonephritis correlates with the severity of disease. Moreover, immune complexes are of diagnostic importance where infections with a chronic development or neoplastic diseases are concerned. The choice of IC test system should incorporate their essential biological functions and identify those IC that activate the complement cascade both by the classical and the alternative route. The detection of IC bound C3 cleavage products (C3b, C3bi, C3d) represents the key to identification of a wide range of IC. Of the presently available methods Raji cell test, conglutinin- and anti C3-IC assay, on critical appraisal, the anti C3-IC assay represents the most applicable way of defining complement binding IC. The advantage of this system is that appreciable disturbances and limitations that influence other systems do not affect the antigen-antibody reaction which is the core of the anti C3 assay.

Antigen-Antibody Complex↗

Electric-field-induced fusion of enzyme-treated human red cells: kinetics of intermembrane protein exchange.

Fusion of neuraminidase or trypsin pretreated human erythrocytes and untreated cells was performed. The obtained doublets had a permanent dipole moment which disappeared as a function of time. Since the dipole moment disappearance is due to protein interdiffusion the lateral diffusion constant may be determined. This was performed by fixing fused cells in different time intervals following the electric pulse and by measuring the reorientation of fixed cell doublets in a static electric field. A surprisingly high diffusion constant was obtained, about 3 X 10(-9) cm2/s. A delay in interdiffusion kinetics was observed in neuraminidase treated cells; this may be due to a restricted growth of the fusion site perimeter. Our data demonstrate that protease treatment promotes electric-field-induced cell-to-cell fusion.

Cell Fusion↗

Working posture and musculoskeletal problems of video display terminal operators--review and reappraisal.

In order to minimize the stresses on the musculoskeletal system, attempts have been made to develop design guidelines for video display terminal workstations. Evaluations of VDT workstations reveal that many of the health problems experienced by operators might be attributed to awkward postures caused by lack of consideration of these guidelines. In other cases, it may be a matter of specific individuals not fitting "average" workstations. This has led to an increasing emphasis on designing adjustable workstations which can be adapted to the individual worker's needs. Even when guidelines are followed and workstations are adjusted to fit individuals, a variety of postural complaints may arise. One of the most important contributing factors is the constraint which is typically placed on the posture of the VDT operator. Many tasks lead to prolonged static positioning of the back, neck, arms and legs; producing rapid fatigue and increasing the risk of chronic problems. Another factor which must be considered is the effect of repetitive motion patterns which could lead to disorders in the muscles, tendons, nerves and joints. Finally, the effects of job pressures must not be overlooked as a potential contributing factor in postural complaints.

Bone Diseases↗

Lectin-defined cell surface glycoconjugates of pancreatic cancer cells and their nonmalignant counterparts.

Alterations of cell surface carbohydrates of human pancreatic cancer cells from long-term cultures (COLO 357, RPMI 7451, PC 103, PC 107) were assessed ultrastructurally by use of an array of lectin-enzyme conjugates, and compared with lectin-defined changes of glycoconjugates on human pancreatic tissue sections of normal and various pathological conditions. Ulex europeus and, to a lesser degree, Lotus tetragonolobus lectin binding indicate that L-fucose-containing glycoconjugates are expressed predominantly on pancreatic cancer cell surfaces, but not, or restricted to intracytoplasmic structures, on nonmalignant pancreas cells. A comparable binding pattern to pancreatic carcinoma cells is found for Phaseolus vulgaris lectin. This is in contrast to the results with soy bean lectin, the reactivity of which was not restricted to cancer cell surfaces, and with Helix pomatia lectin, which did not bind to pancreatic cancer cells at all, although the latter three lectins possess similar sugar specificities. Between the long-term-cultured malignant pancreas cells differences were observed concerning the binding of wheat germ and pokeweed lectin. Besides, qualitative assets of lectin-binding absorption analyses elaborated quantitative differences in the expression of lectin-defined glycoconjugates on pancreatic cancer cell surfaces.

Carbohydrates↗

The intrathymic microenvironment: expression of lectin receptors and lectin-like molecules of differentiation antigens and MHC gene products.

The expression of MHC products, differentiation antigens and lectin receptors has been investigated in the various cell types populating different compartments of the thymus. The ultrastructural classification of suspended thymic epithelial cells was facilitated by using a technique that preserves cortical nursing cells or medullary epithelial cell clusters. A subset of peanut lectin positive lymphocytes could be distinguished by their ability to bind soybean lectin also. This subset corresponds to the large proliferating lymphocytes that populate the area between the thymic capsule and the cortex. Ia and H-2 D/K antigens could be detected on nearly all epithelial and lymphoid cells. Expression of H-2 antigens, however, is more pronounced on medullary epithelial cells. T-cell differentiation antigens such as Thy-1 and Lyt-1 could be demonstrated not only on lymphocytes, but, interestingly enough, on cortical epithelial cells as well. These latter cells, in addition, exhibit a cell membrane-bound lectin with a specificity for D-galactose which might well be the structure responsible for binding the galactosyl residues of the peanut lectin receptor of thymic lymphocytes. Binding sites for a large set of lectins could be demonstrated on both, thymic lymphocytes and epithelium. The intrathymic differentiation pathway of T-lineage cells is discussed with regard to those lymphocytic and epithelial cell surface structures considered to enable cellular interaction.

Animals↗