Zum Ursprung der Normalantikörper

Zusammenfassung In allen Studien mit modernen Methoden der keimfreien Forschung, der Serologie und der Genetik hat sich als die Ursachenachweisbarer normaler Hämagglutinine immunogene Stimulation beweisen oder hochwahrscheinlich machen lassen. Ererbt ist die Fähigkeit, Antikörper zu bilden. Genetische Faktoren dürften bei der Induktion der Antikörpersynthese durch Antigene bedeutungsvoll sein. Auch ist nach dem heutigen Stande des Wissens die primäre Globulinstruktur genetisch bedingt.Die eigenen hier referierten Versuche wurden von der U.S. National Science Foundation durch Grant G-3516 und durch Grant DA 49-007-MD-463 der Research and Development Division, Office of the Surgeon General, Department of the Army, Washington, D.C., unterstützt.Established Investigator of the American Heart Association.     

Monoclonal xenogeneic antibodies to murine cell surface antigens: identification of novel leukocyte differentiation antigens.

Hybrid myeloma cell lines secreting monoclonal antibodies to mouse cell surface antigens have been prepared. Spleen cells from a DA rat immunized with B10 mouse spleen cells that had been enriched for T cells were fused to cells from a nonsecreting mouse myeloma line (NSI). The presence in the culture supernatants of antibodies binding to mouse spleen cells was tested by a binding assay with 125I-labeled anti-rat IgG. From a large number of positive cultures, ten independent hybrid clones were purified, each secreting a different antibody. Each antigenic target was analyzed by (a) gel electrophoresis of immunoprecipitated 125 I-labeled cell surface molecules, (b) heat stability, (c) strain and species distribution and (d) cross-inhibition of binding of different monoclonal antibodies. It was concluded that the ten monoclonal antibodies regognized four types of antigen. One was the heterophile, heat-stable, Forssman antigen. The second (mol.wt. 210 000) appears to be a major 125I-labeled lymphoid cell surface protein. The third, a minor component of spleen cells, was precipitated as two polypeptides of mol.wt. 190 000 and 105 000. Five IgG-secreting clones identify the fourth antigen, a heat-stable, possibly glycolipid component expressed on mouse red blood cells and also on thymocytes. Cross-inhibition studies suggest that these last monoclonal antibodies bind to overlapping, but not identical, determinants. The class and chain composition of the monoclonal antibodies were studied by gel electrophoresis, isoelectric focusing and ability to lyse red blood cells and thymocytes.     

Temperament as a moderator of children's stressful experiences

Data on 158 children, six and nine years old, are analyzed for the relationship between stress and behavior. Undesirable life events and intense "hassles" were particularly correlated with behavioral symptoms. Statistically, temperament appears to moderate this influence but, lacking appreciable variance of symptoms in the models including these interaction effects, the more parsimonious main-effects concept may be more useful.     

The Functional Status of the ACL in Varus OA of the Knee: The Association With Varus Deformity and Coronal Tibiofemoral Subluxation

BackgroundThe present article analyzes the association of the functional anterior cruciate ligament (ACL) status and the overall varus deformity and coronal tibiofemoral subluxation (CTFS) in varus OA of the knee.MethodsOne hundred consecutive knees with varus OA in 84 patients were prospectively included. Knees were divided into two groups, in accordance with the ACL status (functionally sufficient or insufficient). All included patients were potential candidates for unicompartmental knee arthroplasty with predominantly medial compartment OA. Knees with Kellgren/Lawrence ≥ grade 3 in the lateral compartment were excluded leaving 79 knees to be included in this study. Mechanical varus deformity and CTFS were evaluated on AP radiographs and valgus stress radiographs, and compared between the two groups.ResultsKnees with a functionally insufficient ACL had significantly more varus deformity on hip-to-ankle AP standing radiographs (P = .001) and on valgus stress radiographs (P = .017). CTFS on AP standing radiographs was significantly higher (P = .045) in knees with a functionally insufficient ACL. Seventy-three percent (8/11) of the ACL-insufficient knees had a varus deformity of ≥10° and 64% (7/11) of ACL-insufficient knees had CTFS ≥ 6mm. By contrast, only one patient (2%, 1/41) with an insufficient ACL had< 10° varus deformity and a CTFS of < 6mm.ConclusionFunctional ACL insufficiency in osteoarthritic varus knees is associated with greater varus deformity and more advanced CTFS. Seventy-three percent of ACL-insufficient knees had a varus deformity of ≥10° and 64% of ACL-insufficient knees a CTFS of ≥ 6mm. In the work-up for medial unicompartmental knee arthroplasty, functional ACL insufficiency is likely in knees with varus deformity of ≥10° and CTFS of ≥ 6mm.     

Anti-Interleukin-6 Therapy Decreases Hip Synovitis and Bone Resorption and Increases Bone Formation Following Ischemic Osteonecrosis of the Femoral Head

Legg-Calvé-Perthes disease (LCPD) is a juvenile form of ischemic femoral head osteonecrosis, which produces chronic hip synovitis, permanent femoral head deformity, and premature osteoarthritis. Currently, there is no medical therapy for LCPD. Interleukin-6 (IL-6) is significantly elevated in the synovial fluid of patients with LCPD. We hypothesize that IL-6 elevation promotes chronic hip synovitis and impairs bone healing after ischemic osteonecrosis. We set out to test if anti-IL-6 therapy using tocilizumab can decrease hip synovitis and improve bone healing in the piglet model of LCPD. Fourteen piglets were surgically induced with ischemic osteonecrosis and assigned to two groups: the no treatment group (n = 7) and the tocilizumab group (15 to 20 mg/kg, biweekly intravenous injection, n = 7). All animals were euthanized 8 weeks after the induction of osteonecrosis. Hip synovium and femoral heads were assessed for hip synovitis and bone healing using histology, micro-CT, and histomorphometry. The mean hip synovitis score and the number of synovial macrophages and vessels were significantly lower in the tocilizumab group compared with the no treatment group (p < .0001, p = .01, and p < .01, respectively). Micro-CT analysis of the femoral heads showed a significantly higher bone volume in the tocilizumab group compared with the no treatment group (p = .02). The histologic assessment revealed a significantly lower number of osteoclasts per bone surface (p < .001) in the tocilizumab group compared with the no treatment group. Moreover, fluorochrome labeling showed a significantly higher percent of mineralizing bone surface (p < .01), bone formation rate per bone surface (p < .01), and mineral apposition rate (p = .04) in the tocilizumab group. Taken together, tocilizumab therapy decreased hip synovitis and osteoclastic bone resorption and increased new bone formation after ischemic osteonecrosis. This study provides preclinical evidence that tocilizumab decreases synovitis and improves bone healing in a large animal model of LCPD. © 2020 American Society for Bone and Mineral Research (ASBMR).     

31P and 23Na NMR spectroscopy of normal and ischemic rat skeletal muscle. Use of a shift reagent in vivo

23Na NMR spectroscopy was used 1, to define the distribution of the shift reagent for cations, triethylenetetraminehexaacetatedysprosium(III), DyTTHA3-, in the living rat; 2, to define the characteristics of the Na resonances reporting intra- and extracellular Na+ in skeletal muscle in vivo; and 3, to calculate the Na+ concentrations in the intra- and extracellular spaces of the gastrocnemius muscle during well-perfused and ischemic conditions. The concentration of DyTTHA3- infused intravenously into the jugular vein of the living rat reached a maximum value of 8-9 mM in the extracellular space of the muscle after ca 40 min of infusion. This allowed excellent discrimination of extra- and intracellular Na signals (Nao and Nai, respectively) and did not spoil the resolution of concurrent 31P NMR spectra. Infusion of shift reagent changed neither hemodynamic performance of the rat nor the high-energy phosphate content of skeletal muscle. Shift reagent enters ca 15% (v/w) of the rat body weight; this corresponds to almost all of the "fast" or rapidly permeable extracellular space. It is excreted from the body with a pseudo-first order rate constant of 0.0158 min-1. In resting muscle, we estimate that [Na+]i is 3-5 mM and, in muscle perfused with the sodium salt of the shift reagent, that [Na+]o in the fast exchangeable extracellular space is 166 mM. During 11 h of ischemia at 37 degrees C, the area of the Nai+ signal area monotonically increased sixfold. Based on estimates for maximum changes in fluid shifts reported by the decrease in the area of the Nao signal area, we calculate that the lower limit for [Na+]i after 11 h of ischemia is 27 mM. The NMR-visibility factors for the extracellular and intracellular Na+ signals are essentially the same. This study demonstrates that the shift reagent DyTTHA3- is acutely non-toxic and that the 23Na NMR spectra obtained can be used to quantitate [Na+]o and [Na+]i in tissues in vivo. Using this technique, we found that the transmembrane sodium gradient fell from ca 35 in well-perfused skeletal muscle to less than 6 during prolonged ischemia.     

Second International Congress of the European Association for Endoscopic Surgery (E.A.E.S.) Madrid,Spain, September 14–17, 1994 Video Presentations

Abstracts

Second International Congress of the European Association for Endoscopic Surgery (E.A.E.S.) Madrid, Spain, September 14–17, 1994 Video Presentations     

Differential expression of Neu messenger-RNA and protein in hamster-kidney and estrogen-induced kidney tumors

An inverse relationship between the expression of the neu oncogene and estrogen receptors has been observed in breast cancer patients. In this study, we examined neu expression in the estrogen-induced and -dependent hamster kidney tumors, in kidney and in controls to evaluate the usefulness of this animal model far studying the regulation of genes important in hormonal cancer. The expression of neu mRNA was analyzed by Northern analysis and Neu oncoprotein localization by immunocytochemistry. The Neu oncoprotein was detected in several segments of proximal and distal kidney tubules, the loops of Henle and the parietal epithelial cells of Bowman's capsule but not in the tumor. neu mRNA was expressed in renal tissue after estrogen treatment and in untreated controls, but not in kidney tumors. The absence of Neu oncoprotein and mRNA from those cell types that have previously been shown to overexpress estrogen receptors in response to estrogen, suggests that the estrogen receptor and neu genes are interdependent in this tumor system, which may thus be a useful animal model for studying the regulation of neu by estrogens.     

Executive control functions in task switching: evidence from brain injured patients

Executive mechanisms involved in task switching were studied in 18 brain injured patients. The patients had to rapidly switch back and forth between two visual classification tasks and the analyses focused on switch costs, (i.e., performance differences between switch and no-switch trials), and on interference effects, (i.e., processing costs imposed by the presence of interfering stimulus attributes). The patients were grouped according to the side of the brain lesion. Patients with left brain damage (LBD) showed higher switch costs than patients with right brain damage (RBD). These group differences were attributable to disproportionally high switch costs in patients with LBD and language or speech disorders. This result suggests that the efficiency of suppressing internal interference from a recently activated task set depends on the availability of verbal representations of the upcoming task. Patients with RBD showed higher interference from external task sets. This effect was not affected by language or speech disorders. The overall results argue for a fractionation of executive functions to protect against interference from internal and external sources in task switching.