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G Dietrich

Publications and source records attributed to G Dietrich.

At least 19 recordsLinked to original sources
PubMed1992

Origin of anti-idiotypic activity against anti-factor VIII autoantibodies in pools of normal human immunoglobulin G (IVIg).

Therapeutic preparations of polyspecific IgG obtained from plasma pools of a large number of normal donors (IVIg) express anti-idiotypic activity against a wide spectrum of natural and disease-associated autoantibodies. The present study investigated the origin of anti-idiotypic activity against autoantibodies to factor VIII. The neutralizing activity of pools of IgG against patients' anti-factor VIII autoantibodies was not influenced by the presence of individuals with natural anti-factor VIII antibodies among donors contributing to the pool. A higher frequency of neutralizing antibodies against anti-factor VIII autoantibodies was found in aged donors as compared with young adults and in pools of IgG from multiparous women as compared with IgG from random donors. Pooling IgG from several donors synergistically enhanced the inhibitory activity of the pools. Thus, a neutralizing activity against anti-factor VIII autoantibodies was detected in pools of IgG of as few as two to four donors of whom individually tested IgG did not exhibit inhibitory activity against anti-factor VIII autoantibodies. These observations suggest that aged donors and multiparous women may be privileged sources for the anti-idiotypic activity of IVIg against autoantibodies and emphasize that the expression of anti-idiotypic activity in IVIg results from a synergistic participation of anti-idiotypes from each donor contributing to the pool.

Adult↗
PubMed1992

Natural antibodies to factor VIII (anti-hemophilic factor) in healthy individuals.

Spontaneous inhibitors of factor VIII (FVIII) are pathogenic IgG autoantibodies of restricted isotypic heterogeneity found in the plasma of patients presenting with bleeding episodes and low levels of FVIII. We now report the presence of a natural FVIII-neutralizing activity in 85 of 500 plasma samples (17%) from healthy donors. FVIII-inhibitory activity was present in F(ab')2 fragments of purified IgG and was dose-dependent. The titer of anti-FVIII antibodies in normal plasma ranged between 0.4 (threshold of detection) and 2.0 Bethesda units. Anti-FVIII IgG was also detected in normal plasma by using an ELISA. Anti-FVIII antibodies from healthy individuals did not exhibit restricted isotypic heterogeneity. Mean levels of FVIII activity did not differ significantly between individuals with and without detectable anti-FVIII antibodies in plasma. Natural anti-FVIII IgG inhibited FVIII activity in pools of normal plasma and in plasma of certain donors in the pool but did not inhibit FVIII activity in autologous plasma. These observations demonstrate that polyclonal IgG antibodies against procoagulant FVIII are present in healthy individuals. The antibodies are natural IgG autoantibodies and/or antibodies directed against epitopes associated with a so far unidentified allotypic polymorphism of the human FVIII molecule.

Adult↗
PubMed1992

A V region-connected autoreactive subfraction of normal human serum immunoglobulin G.

Mouse and human natural IgM autoantibodies have been shown to be polyreactive and "connected" through V region-dependent interactions. In the present study, we have identified a connected subfraction of normal human serum IgG by using affinity chromatography of F(ab')2 fragments of pooled IgG (IVIg) or of IgG from a single donor on Sepharose-bound F(ab')2 fragments of the same source of IgG. The connected fraction of IgG exhibited a high content of autoantibodies directed against a wide panel of evolutionarily conserved self antigens and of self antigens that may be targets of autoantibodies in autoimmune diseases. Connected IgG also contained higher amounts of antibodies directed against commonly encountered microbial antigens than unfractionated IgG. The connected fraction did not, however, differ from unchromatographed IgG nor from non-connected IgG in its content of antibodies to vaccinal antigens and to distant foreign antigens. Thus, in humans as in mice, connectivity is a prominent feature of autoantibodies. Our observations are suggestive of a tight control by IgG of the expressed autoreactive repertoire in healthy individuals and strengthen the concept that the therapeutic infusion of pooled normal IgG (IVIg) may be effective in autoimmune diseases by bringing to patients normal regulatory components of the immunoglobulin network.

Autoantibodies↗
PubMed1992

Heel-off perturbation during gait initiation: biomechanical analysis using triaxial accelerometry and a force plate.

This study analyzes the movements of the hips, shoulders and of the body center of gravity before and at heel-off, when step execution begins to initiate gait from an upright posture. The heel-off movement was considered as a dynamic perturbation induced by the stepping movement. The experimental paradigm used for studying this perturbation was the single-step movement, in which the initial posture and voluntary movements are identical to those of gait initiation. Data were collected from accelerometer recordings of the triaxial accelerations at the joints of the upper part of the body, and by calculating the triaxial accelerations of the center of gravity using force plate measurements. The resultant vectors were used to establish and compare the magnitude and direction of the accelerations at different joints, and from them, the roles of the pelvis and the scapular girdles with respect to the objectives of the gait movement.

Acceleration↗
PubMed1992

Modulation of autoimmunity by intravenous immune globulin through interaction with the function of the immune/idiotypic network.

Infusion of intravenous immune globulin (IVIG) has resulted in clinical improvement and/or a fall in autoantibody titer in a number of autoimmune diseases in which direct or indirect evidence suggests a pathogenic role for autoantibodies. IVIG may react with disease-associated autoantibodies through idiotypic interactions as shown by the following lines of evidence: (1) inhibition of autoantibody activity in F(ab')2 fragments of patients' IgG by F(ab')2 fragments of IVIG; (2) retention of autoantibodies on affinity columns of Sepharose-bound F(ab')2 fragments of IVIG; and (3) recognition of the same idiotypic determinants on autoantibodies by heterologous anti-idiotypic antibodies and by IVIG. IVIG also interacts with idiotypic determinants on natural autoantibodies as indicated by the binding of monoclonal IgM secreted by Epstein-Barr virus-transformed normal human B cells to F(ab')2 fragments of IVIG and by idiotypic interactions between normal IgG antibodies within the IVIG preparations. Infusion of IVIG into patients with autoimmune diseases alters the kinetic behavior of disease-associated and natural autoantibodies of unrelated specificities. It is our view that IVIG is effective in autoimmune diseases not merely by a passive transfer of suppressive anti-idiotypes, but rather by imposing a normal function on the defective network in autoimmune patients. The intrinsic complexity of IVIG would provide a more logical (physiological) rationale for immunoregulatory therapy of autoimmune disease than idiotype-specific suppression.

Animals↗
PubMed1992

Filtration of buffy coat free red cell concentrates in additive solution.

Leukocyte poor RCC's (LP-RCC) are indicated in chronically transfused patients in order to prevent non-hemolytic transfusion reactions and HLA alloimmunization. In this study buffy coat free red cell concentrates (BCF-RCC) in additive solution (SAG-M) stored for four weeks were leukocyte depleted by filtration with three different filter systems (Erypur Optima (E), Sepacell R500 B (S) and, Pall RC, 50 TM (P)). The BCF-RCC's were prepared using 'bottom and top (BAT)' systems and automatic separation containing about 20% leukocytes and 5% platelets of fresh whole blood. The leukocyte concentration could be reduced to less than 5 x 10(6) per RCC with all filter systems equally: Leukocytes/RCC's: E .58 +/- .94, S .36 +/- .55, P .55 +/- .69 x 10(6). The leukocyte depletion was even in case of filtering two RCC's through one filter (double filtration) efficient enough in order to keep leukocyte contamination below the 'critical immunogenic load for leukocytes (CILL)'. But significant differences concerning the damage of red cells (free hemoglobin, LDH, HBDH) were measured which were even considerable: free hemoglobin E = 3.69 +/- 2.28, S = 1.31 +/- 1.24, P = 3.58 +/- 2.34 g/l. Double filtration was only performed with filter system S showing the best blood compatibility. But the second BCF-RCC also showed considerable hemolysis. Therefore, double filtration of RCC's only seems to be indicated under optimal conditions with blood compatible filters for selected patients. Bed side filtration cannot be recommended because of the risk of hemolysis that makes quality control necessary.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Component Removal↗
PubMed1992

Superiority of gel centrifugation in antibody screening and identification.

We report on the direct comparison of gel centrifugation technique and tube testing for antibody screening (ABS) under controlled routine conditions. 3,000 blood samples were screened for antibodies (AB) by gel centrifugation (ID-System, bromelin 37 degrees C and room temperature, indirect antiglobulin test with LISS) and a sensitive tube test (TT; bromelin two-phase test, 37 degrees C and room temperature, and indirect antiglobulin test with 22% bovine albumin) in parallel. By ID significantly more relevant and potentially hemolytic AB (51 vs. 35 AB/1.7 vs. 1.2%) could be detected: anti-E 4, -C 1, -D 4, -CW 2, -c 2, -Jk(a) 2, -Jk(b) 1. Eleven of these even remained negative in TT when retested with increased sensitivity and taking additional (homozygous) test cells. In addition, naturally occurring but rarely hemolytic AB (35 vs. 23 AB/1.2 vs. 0.8%) were more frequently detectable by ID: anti-Le(a) 6, -Le(b) 2, -P1 6. In contrast, only two AB were only positive in TT: anti-Le(a) 1, -Le(a, b) 1. The main disadvantage of the ID was its frequent positivity (7.7 vs. 4.3%) due to irrelevant cold AB (anti-I, -HI, -H) and unspecific factors. This can be partly reduced by omission of the bromelin test at room temperature (ID 3.0%, TT 1.5%) as the detection of relevant AB is not affected. The frequency of naturally occurring AB was still the same as in TT (0.7%) when bromelin at room temperature was omitted in both techniques. Further advantages of the ID are simplicity, small volumes of sera and reagents, and easy evaluation.

Blood Grouping and Crossmatching↗
PubMed1992

[Filtration of buffy coat-free erythrocyte suspensions in additive solution].

Buffy coat-free red cell concentrates in SAG-M (RCC) were produced by BAT system (leukocyte content 132 x 10(6)/RCC). They were stored for 4 weeks and filtered by Erypur Optima (E), Sepacell R 500 B (S) und PALL RC 50 TM (P). Leukocyte depletion was very effective (E: 0.56 x 10(6)/RCC; S: 0.36 x 10(6)/RCC; P: 0.55 x 10(6)/RCC) but hemolysis was remarkable (E: 301 +/- 195; S: 127 +/- 123; P: 368 +/- 256 mg/RCC). Therefore preparation of two RCC per filter was only acceptable with S. In S and P loss of red cells was tolerable (E: 90.5; S. 41.8; P: 38.2). In contrast, E should be rinsed with sodium chloride at the end of the preparation. In E and S filtration times were short without additional pressure (E: 6.6 min; S: 4.7 min; P: 20.3 min). We conclude from our results that the use of buffy coat-free red cell concentrates in additive solution considerably reduces the problems of filtration, e.g. storage interval, leukocyte reduction, hemolysis, filtration flow. Despite this, bedside filtration is not recommended because quality assurance is necessary.

Blood Component Transfusion↗
PubMed1992

[Production of rejuvenated and stable, leukocyte depleted erythrocyte concentrates using the heated centrifugation method].

We report on an alternative to filtration for the preparation of leukocyte-poor red cell concentrates (LP-RCC). It is based on the method of Schneider. Using RCC with buffy coat it is comparably effective in leukocyte reduction [98.3 +/- 1.0%, (3.7 +/- 2.6) x 10(6) leukocytes] and more effective in platelet reduction (96.9 +/- 2.5%). Addition of PAGGS-M before heating (30 min, 37 degrees C) as well as after preparation significantly reduces hemolysis (free hemoglobin, LDH, HBDH) and improves the quality of the LP-RCC (ATP, 2,3-DPG) during storage for 24 h after preparation. LP-RCCs prepared with PAGGS-M after 6-day storage show still better quality than before preparation and about the same quality as LP-RCCs 24 h after conventional preparation with saline solution. In conclusion, by use of PAGGS-M and sterile docking LP-RCCs of adequate quality for 6-day storage can be prepared, improving the supply of the patients concerned.

Adenine↗
PubMed1992

[Superiority of the gel centrifugation method (ID System) in detection of erythrocyte antibodies].

We report on the direct comparison of gel centrifugation technique and tube testing for antibody (AB) screening (ABS) under controlled routine conditions. 3,000 blood samples were screened for AB by gel centrifugation (ID-System, bromelin 37 degrees C and room temperature, indirect antiglobulin test with LISS) and a sensitive tube test (T; bromelin two-phase test 37 degrees C/room temperature and indirect antiglobulin test with 22% bovine albumin) in parallel. By ID significantly more relevant and potentially hemolytic AB (51 vs. 35 AB/1.7 vs. 1.2%) could be detected: anti-E 4, anti-C 1, anti-D 4, anti-CW 2, anti-C 2, anti-Jk (a) 2, anti-Jk (b) 1. 11 of these even remained negative in tube test when retested with increased sensitivity and taking additional (homozygous) test cells. In addition, naturally occurring but rarely hemolytic AB (35 vs. 23 AB/1.2 vs. 0.8%) were also more frequently detectable by ID: anti-Le (a) 6, anti-Le (b) 2, anti-P1 6. In contrast, only two AB were only positive in T: anti-Le (a) 1, anti-Le (ab) 1. The main disadvantage of ID was its frequent positivity (7.7 vs. 4.3%) due to irrelevant cold AB (anti-I, anti-HI, anti-H) and unspecific factors. This can be partly reduced by omission of the bromelin test at room temperature (ID 3.0%, T 1.5%) as the detection of relevant AB is not affected. The frequency of naturally occurring AB was still the same as in T (0.7%) when bromelin at room temperature was omitted in both techniques. Further advantages of ID are simplicity, small volumes of sera and reagents and easy evaluability.

Blood Group Antigens↗
PubMed1992

Progress in veno-venous long-term bypass techniques for the treatment of ARDS. Controlled clinical trial with the heparin-coated bypass circuit.

Extracorporeal CO2 removal combined with low-frequency positive pressure ventilation (ECCO2-R LFPPV) is a new therapeutic approach in treatment of ARDS. The main problem during long-term extracorporeal support is anticoagulation and related bleeding problems. We conducted a prospective, randomized and controlled clinical trial in 18 patients to compare the effect of the non-heparin-coated (Scimed = group 1) with the heparin-coated (Carmeda = group 2) extracorporeal circuit on clinical course and complication rate. In group 2 the daily blood loss, the amount of substituted red cells and the i.v. heparin dose were significantly lower than in group 1. Bleeding complications were less and more patients survived in group 2. The disadvantage of the hollow fiber oxygenators in the heparin-coated system was plasma leakage, which was more frequent in patients with pancreatitis and hyperbilirubinemia.

Adolescent↗
PubMed1991

Intravenous immunoglobulin in the treatment of spontaneously acquired factor VIII:C inhibitors.

Intravenous immunoglobulin (IV Ig) is useful in most patients with spontaneous factor VIII:C (FVIII:C) inhibitors, but some complete failures also are observed. Among patients responding to this therapy, decreases in FVIII:C autoantibody titer occurs within 24-48 hours and may lead to suppression of inhibitor activity. The prolonged response observed in some cases suggest an effect on autoantibody synthesis. The immediate decrease in FVIII:C inhibitory activity after IV Ig infusion indicates a direct interaction between IV Ig and the autoantibody. This effect is reproducible in vitro by mixing the patient's plasma and Ig at an appropriate molar ratio, which differs in each patient. Similarly, incubation of Ig with F(ab)'2 fragments of a patient's IgG and Ig reproduces inhibition, and this result indicates that the interaction is mediated by antigen binding sites (epitopes) on the immunoglobulins. The suggestion is that an idiotype- anti-idiotype mechanism must be at work. The origin of such anti-idiotypes in Ig prepared from pooled plasma of several thousand blood donors is unclear. The F(ab)'2 fragments were prepared from individual blood donors and tested in similar experiments with F(ab)'2 fragments of three distinct spontaneous FVIII:C inhibitors. The plasma level of anti-idiotypic antibodies reacting with FVIII:C inhibitors varied according to age and gender.

Antibodies, Anti-Idiotypic↗
PubMed1991

Population dynamics of natural antibodies in normal and autoimmune individuals.

We have measured the quantities of naturally occurring autoantibodies in the serum of normal, unmanipulated individuals. These changes over time following broad-band complex dynamical patterns that are similar in mouse and man. The patterns more likely reflect the network architecture of the natural antibody repertoire, regulating the activation and decay of individual clones. The temporal changes of both disease-specific and nonspecific autoantibodies are consistently modified in autoimmune individuals.

Animals↗
PubMed1991

Evidence for a restricted idiotypic and epitopic specificity of anti-thyroglobulin autoantibodies in patients with autoimmune thyroiditis.

Anti-thyroglobulin (TG) autoantibodies from patients with autoimmune thyroiditis express a cross-reactive alpha idiotype (Id) termed T44 which is not expressed by IgG from normal individuals. The present study demonstrates that the expression of the T44 Id is strongly associated with the recognition by anti-TG autoantibodies of a specific epitopic cluster on human TG. The epitopic reactivity of anti-TG autoantibodies was determined using a competitive inhibition assay with a panel of 15 monoclonal antibodies that define six antigenic clusters on TG. All T44+ autoantibodies from patients recognized cluster II, whereas no anti-TG IgG from healthy individuals reacted with this region. Affinity columns of Sepharose-bound intravenous therapeutic immunoglobulins which contain anti-T44 activity, retained both T44 Id-expressing antibodies and a subset of region II-specific anti-TG autoantibodies from patients with Hashimoto's disease. Restricted idiotypic and epitopic specificity may demarcate disease-associated from natural anti-TG autoantibodies, suggesting that qualitative rather than quantitative criteria should be used to identify pathological autoantibodies.

Antibody Specificity↗
PubMed1991

Intravenous immunoglobulins (IVIg) in the treatment of autoimmune diseases.

Intravenous immunoglobulin (IVIg) therapy is increasingly used in autoimmune diseases. Although its efficacy has only been established in a few specific antibody-mediated autoimmune conditions, accumulating evidence on the regulatory role of circulating immunoglobulins in the selection of peripheral B cell repertoires makes it an attractive potential therapeutic option to clinical immunologists. This overview briefly discusses the current use of IVIg in human autoimmune diseases with a particular emphasis on the possible mechanisms by which IVIg could suppress pathological autoimmune responses.

Antigenic Modulation↗
PubMed1991

Transfusion results of platelet concentrates using different cell separators.

115 patients with bone marrow aplasia/hypoplasia received a total of 567 transfusions of fresh HLA-selected platelet concentrates at random from the AS-104 and CS-3000 and, whenever possible, from both separators using the same donor. By daily platelet counting pre and up to seven days post transfusion, the posttransfusional increments per 10(11) platelets transfused were calculated. Fresh platelets collected from the AS-104 showed comparable in vivo recovery at the first day post transfusion but significant better survival compared to those from the CS-3000. This is in line with in vitro studies published before, where we already reported on better in vitro function and morphology. Increased platelet yields and improval of the platelet survival of the PC's from the AS-104 should result in prolonged transfusion intervals. When additionally evaluating a limited number of PC's from the AS-104 stored in teflon bags up to five days before transfusion (n = 12), we did not get favorable results compared to PC's from the CS-3000 stored in polyolefine bags. As this seemed to be due to the geometry of the bags, it was consequently changed in the meantime.

Anemia, Aplastic↗