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W Mempel

Publications and source records attributed to W Mempel.

At least 19 recordsLinked to original sources

Complement activation during storage of blood under normal blood bank conditions. Effects of proteinase inhibitors and leukocyte depletion.

During storage of CPD-A1 preserved whole blood factors of the complement cascade become activated, as evidenced by a rapid increase in the concentrations of C3a-desArg and C4a-desArg. After 10 to 14 days of whole blood storage, the elevations of C3a and C4a levels were highly significant. This increase was paralleled by an increase in the concentration of the lysosomal proteinase elastase from polymorphonuclear (PMN) granulocytes. By contrast, the concentration of the C3 activator complex C4b2b remained unchanged even after 3 weeks of storage. The supplementation of the anticoagulant CPD-A1 with the polyvalent-proteinase-inhibitor aprotinin and the specific elastase-inhibitor eglin C failed to inhibit complement activation, whereas leukocyte depletion could partially abolish the increase of the concentration of C4a, but had no effect on C3a concentrations. These observations support the notion that cleavage of C4 during storage of whole blood is partially leukocyte dependent, whereas the activation of C3 is possibly caused by the activation of the alternate pathway of the complement system by contact of plasma with plastic surfaces.

Aprotinin

Diagnosis of transfusion-associated graft-versus-host disease by genetic fingerprinting and polymerase chain reaction.

A patient with Hodgkin's disease (clinical stage IIIB) received chemotherapy and total nodal irradiation. After the transfusion of filtered packed red cells, this patient developed transfusion-associated graft-versus-host disease (TA-GVHD). The genetic fingerprint of the patient's peripheral blood lymphocytes (PBLs) differed completely from that of her other body tissues. Normally, after transfusion, only the patient's own genetic fingerprints are observed in the PBLs, as exemplified in more than 10 control cases in which the transfused blood had not been filtered before transfusion. No signal bands corresponding to those of the blood donor could be demonstrated in samples of the patient's tissue DNA. Moreover, chimerism was detected in the hybridization pattern of the patient's PBLs on the ninth day after the onset of symptoms. Polymorphic simple repeats in the HLA-DRB gene after amplification by polymerase chain reaction were also investigated, which confirmed the fingerprinting results. The advantages of these methods for the diagnosis of TA-GVHD include the rapid and unequivocal diagnosis as well as the fact that there is no need for the relatives to be HLA typed.

Adult

Intravenous anti-D gammaglobulin for the prevention of rhesus isoimmunization caused by platelet transfusions in patients with malignant diseases.

Previous studies of sensitization to RhD by RhD-positive platelet transfusions in RhD-negative cancer patients have shown different frequencies of alloimmunization (max. 19%). We studied 37 RhD-negative patients who received RhD-incompatible platelet transfusions and simultaneously anti-D-immune globulin. We provide evidence that in this setting RhD-prophylaxis is highly effective in preventing alloimmunization due to RhD antigen, since none of the patients studied developed anti-D. Detection of other red blood cell antibodies than anti-D proves the possibility of immunization in these patients. Prevention of isoimmunization in patients with malignant diseases is recommended especially in young females, since an increasing number of patients are having successful pregnancies, despite prior or even during cytotoxic therapy.

Adult

Effects of leukocyte depletion on the formation of anaphylatoxins in stored whole blood.

As reported earlier, factors of the complement cascade get activated in CPD-A1-stabilized whole blood. As early as after 10 days of storage under normal blood bank conditions the elevations of the concentrations of C3a-desArg and C4a-des-Arg were highly significant. By contrast, the concentration of the C3 activator complex C4b2b remained unchanged even after 3 weeks of storage. Leukocyte depletion partially inhibited the activation of C4 but had no effect on C3a concentrations. Therefore, cleavage of C4 during storage of whole blood seems to be partially leukocyte-dependent, whereas the activation of C3 is possibly due to the activation of the alternate pathway of the complement system by contact of blood to plastic surfaces. Even through the radioimmunologically measured C3a might be inactive as an anaphylatoxin, these observations are of clinical importance since the inactivated C3a-desArg still possesses biological activities such as activation of platelets which may lead to hypercoagulability and thrombosis.

Blood Preservation

[Graft versus host disease with fatal outcome after administration of filtered erythrocyte concentrates].

Transfusion-associated graft-versus-host disease (TA-GVHD) resulting from the engraftment of competent lymphocytes contained in blood products has been well described in immunocompromised patients and more recently in immunocompetent patients. Prophylactic irradiation of blood products prior to transfusion is the most efficient way to prevent TA-GVHD. Standard blood bank measures to reduce mononuclear cell contamination in red blood cell units, such as freezing, washing and filtration, may reduce the number of viable lymphocytes to prevent immunizations. However, it is unknown whether the depletion of leukocytes with these techniques would decrease the risk of TA-GVHD. In this report we describe the first case of TA-GVHD following transfusion of filtrated red blood cells given to a patient receiving cytotoxic therapy for Hodgkin's disease.

Adult

Decreased formation of the complement component C4A in leukocyte-depleted stored whole blood.

As reported earlier, factors of the complement cascade get activated in CPD-A1-stabilized whole blood. While leukocyte depletion inhibited partially the activation of C4, it had no effect on C3a concentrations. Therefore cleavage of C4 during storage of whole blood seems to be partially leukocyte-dependent, whereas the activation of C3 is possibly due to the activation of the alternate pathway of the complement system by contact of blood to plastic surfaces. Even though the radioimmunologically measured C3a might be inactive as an anaphylatoxin, these observations are of clinical importance since the inactivated C3a-desArg still possesses biological activities, like activation of platelets which may lead to hypercoagulability and thrombosis.

Blood Preservation

[Combination of a simple hollow fiber system with leukocyte filter for production of leukocyte depleted erythrocyte concentrates and plasma].

Leukocyte-depleted red cell concentrate (RCC) and plasma were separated by a hollow fiber filter system combined with a leukocyte filter without any additional devices. The RCC with 100 ml additive solution had a weight of 329 g; hematocrit was 0.55, free hemoglobin 16 mg/dl; leukocytes were (0.6 +/- 0.6) x 10(9)/l. The plasma (268 g) contained 5.4 g/dl of total protein, and only a few blood cells; clotting factor VIII activity 75%, all satisfying the guidelines.

Blood Component Removal

[Attempts in developing a standardized test system of immunologic reactivity].

Stimulation of lymphocytes with mitogens and antigens is an established model for in vitro testing of immunoreactivity. Due to the great variability of blastogenic response the interpretation of these results is difficult. Our results suggest that multivariate experiments and statistics improve the interpretation.

Antigens, Bacterial

[Strong and weak histocompatibility antigens and immune response].

In blood samples of 88 healthy donors various red cell, HLA-A, -B, -Cw and -Dr antigens were determined by standard methods. Lymphocyte reactivity was measured by 3H-thymidine uptake into DNA of lymphoblastic cells stimulated by 14 different mitogens and antigens. Cluster analysis confirmed by t test and F test defined 3 distinct clusters of lymphocyte reactivity. Cluster 1 in 70% [relative risk (r.r.) 109, p < 0.001] and cluster 3 in 92% (r.r. 33, p < 0.01) showed significantly different cumulations of 3 or more increased characteristic red cell and HLA antigens. Our data suggest that the patterns of both red cell and HLA antigens play a major role in defining immunoreactivity.

HLA Antigens

[Incidence of the detection of erythrocyte antibodies in relation to screening test cells].

A variety of antibody screening tests are available to detect immunization in patients' sera. However, antibodies can be observed only if corresponding antigens are present on test cells used by an antibody screen. By comparing available test cell kits of different manufacturers we revealed various specificities of antigens present or absent on these cells. Using by an antibody screen Wr(a+), Co(b+) and Kp(a+) test cells additionally to available test cells, we detected in 1000 sera of patients 13 anti-Wr(a) and 1 anti-Co(b) besides 17 antibodies with different specificities.

Autoantibodies

Functional characterization of canine lymphocyte subsets.

Functional characterization of subsets of T lymphocytes is essential for transplantation studies in dogs, as it is in other species. We studied the function of T cells separated by two mouse monoclonal antibodies recognizing complementary subsets--an antibody directed to canine T cells (MdT-P1) with an up-regulating function, and an antibody directed to human CD 8 (MT811) that cross-reacts with down-regulating canine T cells. Immunorosetting with sheep red blood cells and Percoll gradient allowed us to study depleted and enriched fractions. Their function was tested in mixed lymphocyte culture (MLC), cell-mediated cytotoxicity (CML), and coculture with B cells in a hemolytic plaque assay (PFC). In MLC, MdT-P1-positive cells showed a high proliferative response, and MT811-positive cells responded poorly to allogeneic cells. Vice versa, MT811- negative cells responded strongly, and MdT-P1-negative cells were poor responders but strong stimulators. Effector cells of CML were separated following 8 days of culture and prior to mixing with target cells. Enriched and depleted fractions with either antibody showed low cytotoxic activity as compared with unseparated cells. When added to unseparated effector cells MT 811-positive cells suppressed cytotoxicity. B cells were obtained by rosetting with staphylococcal protein A (SPA). Their immunoglobulin production was studied following 6 days of culture stimulated by pokeweed mitogen in a reverse hemolytic plaque assay. Again, MT 811-positive cells added to the culture suppressed, and MT 811-negative cells enhanced immunoglobulin production. In conclusion, immunorosetting with two monoclonal antibodies allowed us to distinguish subpopulations of canine T cells with up-regulating (helper/inducer) from those with down-regulating (suppressor) activity.

Animals

Cellular immunity in schizophrenic patients before and during neuroleptic treatment.

A possible connection between immunological alterations and schizophrenia has been discussed for many years. We studied 55 schizophrenic patients in an acute stage of illness before they began neuroleptic treatment. 35 patients who showed clinical improvement on neuroleptics, and 51 healthy controls. Our interest was focused on parameters of cellular immunity. We found an increased lymphocyte response to stimulation with pokeweed mitogen (PWM) and phytohemagglutinin (PHA) in patients before neuroleptic therapy and also an increased response to stimulation with PWM and PHA during treatment compared to controls. Stimulation with antigens generally showed a lower lymphocyte response in patients than in controls, but the difference was only significant after stimulation with tuberculin before neuroleptic treatment and after stimulation with varidase, diphteria-toxoid, tuberculin, vaccinia, and rubella during neuroleptic treatment. The number of CD3+ and CD4+ cells, but not the number of CD8+ cells, was increased before and during treatment in comparison to controls. Suppressor-cell activity was reduced in three different suppressor cell assays before and during neuroleptic medication compared to controls. We therefore conclude that alterations of the immunological system which are, as has been demonstrated, not due to treatment with neuroleptics might play a role in schizophrenia.

Adolescent

White cell depletion of single-donor platelet preparations by a new adsorption filter.

A newly developed adsorption filter has been evaluated for the removal of white cells (WBCs) from platelet concentrates. It consists of surface-modified polyester fibers and can be used at the patient's bedside. WBC mean removal rate was 98.8 +/- 0.9 percent, and platelet recovery was 99.0 +/- 0.7 percent. The aggregation curves (ADP, collagen) and hypotonic shock response of platelets were not influenced by the filtration, and the plasma electrolyte and lactate dehydrogenase concentrations were unaffected. Transmission and scanning electron micrographs showed no difference in platelet ultrastructure before and after filtration. Determination of posttransfusion platelet recovery did not reveal any significant difference from that of nonfiltered platelets. The tested filter seems to be a suitable device for WBC depletion of single-donor platelet concentrates at the bedside.

Adenosine Diphosphate

[Detection of high interleukin 6 concentrations in miniaturized human bone marrow long-term cultures].

The long-term bone marrow culture system (LTBMC) consists of an inductive environment provided by a marrow-derived adherent layer which induces pluripotent stem cell replication. The activity of IL-6 was analyzed in micro LTBMC as a potential stem cell regulator. Immediately after initiation there was a tremendous increase in IL-6 activity. With each refeeding, IL-6 levels rose until confluency of the stromal layer was reached at week two to three post initiation. As a working hypothesis for further investigations, we suggest the immediate shift of stem cells after refeeding from a non-cycling into a cycling state might be mediated by the steep increase of IL-6 alone or in cooperation with other factors.

Bone Marrow Transplantation

[The need for thorough infection screening in donors of autologous blood].

To avoid the risk of diseases transmitted by homologous blood, predeposited autologous blood is useful for elective surgical patients. World-wide, there is disagreement over whether complete donor testing should or should not be done on autologous collections. There are a variety of testing concerns which have evolved into reasons for testing all autologous units for the presence of infections disease markers. One of the reasons is the risk of giving the wrong (untested) blood to the wrong patient and transmitting HIV (and thus AIDS) or viral hepatitis. Another stated concern is the risk of creating additional problems in the laboratory by treating some units differently than other units. The argument continues that without this testing, blood bank and hospital personnel may be unnecessarily exposed to blood that has the potential to cause illness. Another justification for testing is given when the blood bank participates in crossover (transfusing blood to recipients other than the autologous donor/patient).

Blood Component Transfusion

[Storage of thrombocyte concentrates: ultrastructural and functional changes].

Optimal storage of platelet concentrates is still an unsolved problem. The present paper demonstrates changes in morphology and function of stored platelets. Transmission microscopy reveals a loss of organelles as well as a progredient destruction of cell membranes during storage. At the same time in vitro aggregability is clearly diminished. Therefore, further investigations seem to be necessary to improve storage conditions of platelets.

Blood Component Transfusion