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Biomedical subjects

L D Petz

Publications and source records attributed to L D Petz.

At least 19 recordsLinked to original sources
PubMed1992

Hemolysis of transfused group O red blood cells in minor ABO-incompatible unrelated-donor bone marrow transplants in patients receiving cyclosporine without posttransplant methotrexate.

Hemolysis most commonly occurs following bone marrow transplant when there is "minor" ABO blood group incompatibility between donor and recipient. The hemolysis has been attributed to destruction of the patient's incompatible erythrocytes by donor-derived anti-A and/or anti-B antibody produced from "passenger" immunocompetent donor lymphocytes. Extraordinary transfusion requirements of group O erythrocytes in a series of patients receiving unrelated minor ABO-incompatible marrow grafts led us to investigate whether this mechanism could account for the extent of hemolysis observed. In seven consecutive minor ABO-incompatible unrelated-donor bone marrow transplant recipients receiving cyclosporine without posttransplant methotrexate, we observed excessive hemolysis. For cases in this index group, a strongly reactive donor-derived ABO blood group antibody was identified coincident with development of hemolysis. Transfusion requirements in the first three patients (26 U of group O erythrocytes each) greatly exceeded the recipient's volume of incompatible erythrocytes, indicating that lysis of transfused group O erythrocytes was also occurring. Pretransplant erythrocyte exchange transfusion with group O erythrocytes performed in the four subsequent patients decreased the severity of hemolysis, but did not prevent it. Among minor ABO-incompatible marrow graft recipients, an analysis of variance demonstrated effects on transfusion requirements due to donor-recipient relationship being unrelated (P less than .002) and the use of posttransplant methotrexate (P = .0001), and there was interaction between these two factors (P less than .001). Bone marrow transplants from unrelated donors resulted in an exaggerated immune response to ABO blood group antigens, which was associated with hemolysis of transfused group O erythrocytes, as well as the patient's ABO-incompatible erythrocytes. This serious complication may be prevented by posttransplant immunosuppression with methotrexate.

ABO Blood-Group System↗
PubMed1992

Selection of platelets for refractory patients by HLA matching and prospective crossmatching.

A multi-site clinical study compared platelets chosen for refractory patients by prospective platelet crossmatching using stored donor platelets and HLA-based selection. Seventy-three patients who were refractory to random-donor platelets received two plateletpheresis components, one chosen by HLA-based criteria and the other by crossmatching. Patients were carefully evaluated to exclude nonimmune factors that could adversely affect transfusion results. Each of the five study sites used a crossmatch procedure with which it had experience. Results from this study indicate the following: 1) The overall rate of successful transfusion was similar when an HLA-based method of donor selection that includes all grades of matching and mismatching was compared to a crossmatch-based method of donor selection. 2) HLA-based selection that restricts recipients to grade A and BU matches was superior to a selection method based upon crossmatching alone. Donor selection based on HLA matching (grades A or BU) was also superior to selection based on any degree of HLA mismatching (grades BX, C, or D). 3) Selection of donors based on HLA-cross-reactive groups (defined by in vitro serologic crossreactivity) was no more successful than that based on grade C and D mismatches and was no more successful than selection by crossmatching alone. 4) Lymphocytotoxic and platelet antibodies were not detected in many of the enrolled patients, even though patients demonstrating nonimmune factors were eliminated from the study. It can be concluded that HLA-compatible (grades A and BU) platelets provide optimal support for refractory patients, but that crossmatch-selected platelets are acceptable as an alternative component.

Adult↗
PubMed1991

Amplification by the polymerase chain reaction of hypervariable regions of the human genome for evaluation of chimerism after bone marrow transplantation.

We combined the polymerase chain reaction (PCR) with oligonucleotide hybridization as a novel and sensitive technique to evaluate posttransplant chimerism. Specific oligonucleotides for hybridization were synthesized homologous to tandemly repetitive core sequences of regions with a variable number of tandem repeats (VNTRs). Polymorphisms at such loci result from allelic differences in the number of repeats. Primers flanking the repeat region of each of the corresponding VNTRs were used for amplification. Recipient and donor pretransplant DNA and recipient posttransplant DNA were amplified. The resultant fragments were analyzed after gel electrophoresis either by hybridization in-gel or after Southern transfer. To confirm our findings, we also performed standard assays of restriction fragment length polymorphisms (RFLPs). Evaluation of 13 selected cases indicated mixed chimerism (4), complete chimerism (5), recurrence of leukemia (2), and endogenous repopulation of hematopoiesis (2) after marrow transplantation. Sensitivity of the method was determined by mixing various proportions of recipient and donor DNA; the limit of detection of the minor component in a mixture was 0.1%. PCR data correlated with RFLP data in all cases except two in which PCR proved more sensitive than RFLP. PCR amplification of VNTRs combined with oligonucleotide hybridization is a novel technique for documenting posttransplant chimerism and has advantages over RFLP analysis: high sensitivity, use of small amounts of DNA (250 ng), ease of preparation of DNA, elimination of need for restriction enzymes, and the ability to complete studies in 2 days.

Base Sequence↗
PubMed1990

Studies of in vitro red cell autoantibody production in normal donors and in patients with autoimmune hemolytic anemia.

The in vitro production of red cell autoantibodies (RBC AuAbs) has been investigated for better understanding of the pathogenesis of autoimmune hemolytic anemia (AIHA). Peripheral blood mononuclear cells (PBMNCs) were isolated and cultured for 14 days with or without added pokeweed mitogen (PWM), autologous RBCs, methyldopa, procainamide, and alpha-methylnorepinephrine. Also, isolated B cells were infected with Epstein-Barr virus (EBV) to produce polyclonal B-cell lines. Supernatants were tested for IgG and IgM RBC AuAbs by use of 125I-staphylococcal protein A (SPA). RBC AuAbs were detected in PBMNC cultures without additives to the culture medium of four of eight patients who had warm-antibody AIHA or a positive direct antiglobulin test (DAT) without hemolytic anemia. In two of these patients, RBC AuAb production was augmented by the addition of PWM, and in two additional patients, RBC AuAbs were detected only after the addition of PWM. Supernatants from PBMNC cultures from three of four normal donors produced RBC AuAbs independent of the presence of PWM; in two of these subjects, PWM augmented production of RBC AuAbs. PBMNC cultures from three DAT-negative patients with systemic lupus erythematosus produced RBC AuAbs, one in the presence of PWM and two in its absence. With one exception, there was no augmentation of AuAb production by the addition to the culture system of autologous RBCs or drugs. EBV infection of B cells from four patients with AIHA and four normal persons yielded B-cell lines secreting RBC AuAbs. The quantity of RBC AuAb after a 24-hour culture of EBV-transformed B cells was significantly greater in cultures from four patients who had AIHA than in cultures from four normal persons.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia, Hemolytic, Autoimmune↗
PubMed1988

Platelet crossmatching.

Explore the source record for details and available documents.

Blood Grouping and Crossmatching↗
PubMed1988

Immunohematologic consequences of major ABO-mismatched bone marrow transplantation.

Twelve of 58 (21%) evaluable patients of blood group 0 who received a bone marrow transplant (BMT) from an HLA-matched sibling of a donor of group A or B developed significant immunohematologic problems in the posttransplant period. Anti-A or anti-B isohemagglutinins persisted for longer than 120 days post-BMT in nine patients and are still present in three patients at days +162 to +605. Red cell production as indicated by a reticulocyte count of greater than 0.5% was delayed to 40 days or more in nine patients, and in five of these was markedly delayed to 170 days or longer. One patient does not as yet have red cell production on day +605 in spite of having had 13 plasma exchanges performed to reduce the anti-B titer. Five patients experienced overt hemolysis, manifested by a sudden drop in hemoglobin of 1.5 to 4 gm/dl (median = 2.5 mg/dl), starting on day +37 to +105 (median = +65), persisting for 10 to 94 days (median = 36 days). Hemolysis and a delay in the onset of erythropoiesis beyond 170 days were more frequent in 30 patients treated with cyclosporine/prednisone than in 28 patients treated with methotrexate/prednisone for graft-versus-host disease prophylaxis. Our data indicate that ABO major mismatched BMT can be associated with significant immunohematologic consequences, some of which occur more frequently in association with cyclosporine administration.

ABO Blood-Group System↗
PubMed1987

Use of DNA restriction fragment length polymorphisms to document marrow engraftment and mixed hematopoietic chimerism following bone marrow transplantation.

We have studied the feasibility of using DNA restriction fragment-length polymorphisms (RFLP) to study marrow engraftment in 27 patients after allogeneic bone marrow transplantation, and have compared these results with those obtained using red blood cell antigens, cytogenetics, and immunoglobulin allotypes. Using highly polymorphic DNA probes, we have documented stable chronic mixed hematopoietic chimerism, have identified transient mixed chimeras, have excluded mixed chimerism with high probability in retrospective studies even when a pretransplant DNA sample was not available, have documented marrow engraftment in the early posttransplant period, and have studied the origin of leukemic cells in patients with recurrent disease. We have evaluated the advantages and disadvantages of several genetic markers and have developed tentative statements concerning the prognosis of patients with mixed chimerism. We conclude that DNA RFLP are powerful and practical genetic markers in bone marrow transplantation studies and that further studies of mixed hematopoietic chimerism are warranted.

Antigens, Surface↗
PubMed1987

Development of a single probe for documentation of chimerism following bone marrow transplantation.

Although numerous genetic markers are available for studying chimerism after bone marrow transplantation (BMT), there remains a need for a practical and highly informative method that is applicable in the early posttransplantation period. Using DNA restriction-fragment-length polymorphisms (RFLPs), we have evaluated the feasibility of developing a single synthetic oligonucleotide probe to study post-BMT chimerism. We have thus tested three candidate probes, termed O-3315-32, O-3315-80, and O-AY-29, that are homologous to tandemly repetitive sequences. Our results demonstrated donor-specific and recipient-specific fragments in 11 of 11 HLA-matched sibling pairs tested using probes O-3315-32 and O-3315-80. When probe O-AY-29 was used, 14 of 17 sibling pairs showed both donor and recipient markers, one had only a recipient marker, and two were identical. We showed that each of the three synthetic probes was effective in documenting donor marrow engraftment, mixed hematopoietic chimerism, the patient's pre-BMT phenotype (by using cultured skin fibroblasts obtained after BMT), and the origin of the malignant hematopoietic cells (i.e., of donor or recipient origin) in patients who developed recurrent hematologic malignancy following BMT. Compared with the use of cloned genomic probes, there are several important advantages to the use of synthetic oligonucleotide probes in studying post-BMT chimerism. Synthetic probes have absolute hybridization specificity and can be designed to suit the purposes of an individual study, since they have adjustable specificity that can be altered by changes in the length of the probe and by changes in the hybridization temperature. A single synthetic probe analogous to several highly polymorphic loci can have a polymorphism information content sufficiently high so that all but a small percentage of BMT patients could be followed easily; for example, if a probe were complementary to three highly polymorphic unlinked loci, it would discriminate approximately 98% of sibling donor/recipient pairs. This would be accomplished using only one restriction-endonuclease digestion and only one gel electrophoresis. Since other genetic markers, e.g., red blood cell antigens, immunoglobulin allotypes, and chromosome analysis, are not uniformly informative and, in some cases, cannot be used in the early posttransplantation period, the use of synthetic oligonucleotide probes for analysis of DNA RFLP is emerging as the method of choice for studies of post-BMT chimerism. This method will allow for the development of new knowledge that has not been possible with previous methods.

Bone Marrow↗
PubMed1987

Mixed hematopoietic chimerism following bone marrow transplantation for hematologic malignancies.

Twenty-nine of 172 patients (17%) who received an allogeneic bone marrow transplant (BMT) from histocompatible sibling donors for hematologic malignancies were mixed hematopoietic chimeras; ie, they had a mixture of donor and host hematopoietic or lymphohematopoietic cells at greater than or equal to 14 days after transplantation. Twenty-four of the 29 mixed chimeras (83%) have remained in continuous complete remission for up to 116 months (greater than 9 years) following BMT. Four of the 29 patients (14%) have had recurrent leukemia, and 7 of the 29 (24%) have had moderate or severe graft-v-host disease (GVHD). Twelve of these 29 patients have persisted as stable mixed chimeras for greater than or equal to 2 years after BMT, whereas other patients converted to all donor-type hematopoiesis. The incidence of mixed chimerism was independent of the pretransplant regimen, the donor or recipient age (less than 20 v greater than 20 years), remission status (first complete remission of acute leukemia and first chronic phase of chronic myelocytic leukemia v later stages of disease), and type of leukemia. Our data indicate that mixed hematopoietic chimerism is not rare after BMT for hematologic malignancies and that its presence is compatible with long-term disease-free survival. Prospective studies of mixed chimerism after BMT are warranted to achieve better understanding of its biologic importance.

Acute Disease↗
PubMed1986

Donor-derived red blood cell antibodies and immune hemolysis after allogeneic bone marrow transplantation.

Six cases of immune hemolytic anemia attributed to donor-derived red cell antibodies after allogeneic bone marrow transplantation (BMT) are reported. In 2/6 cases, severe intravascular hemolysis was seen, 6/6 required increased red cell transfusion, and 1/6 was treated by plasma exchange. All recipients were receiving cyclosporine to prevent graft-v-host disease. Investigations showed that in each case, the donor lacked ABO or Rho(D) red cell antigens present in the recipient. The direct antiglobulin test was positive in 6/6. Relevant serum antibody (anti-A, four cases; anti-B, one case; anti-D, one case) was first detected one to three weeks after BMT. Eluates made from recipient red cells showed the same specificity as serum antibody. Maximum hemolysis occurred nine to 16 days after BMT, suggesting that active production of antibody by "passenger" donor lymphocytes was the likely mechanism of hemolysis, rather than passive transfer of antibody in the marrow infusion. Retrospective analysis of 21 consecutive cyclosporine-treated BMT patients receiving marrow lacking ABO or D antigens present in the recipient showed that (1) 15/18 patients tested had red cell antibody production against recipient red cell antigens; (2) despite the frequent presence of antibody specific for recipient red cell antigens, only 3/21 patients developed clinically significant hemolysis; (3) clinical hemolysis could not be predicted by donor or recipient red cell antibody titers. We conclude that although red cell antibody against recipient antigens is frequently produced after minor ABO and D mismatched BMT in cyclosporine-treated recipients, only 10% to 15% of cases develop clinically significant immune hemolysis. The data presented show that the most likely source of antibody is "passenger" donor lymphoid cells.

ABO Blood-Group System↗
PubMed1986

Immune response to moxalactam in rabbits and in humans.

Three of 23 New Zealand white rabbits immunized with moxalactam or bovine serum albumin (BSA)-moxalactam conjugates produced specific antimoxalactam antibodies. Rabbits that produced antimoxalactam had been immunized, by a novel approach, with heat-aggregated BSA-moxalactam conjugates containing Corynebacterium parvum as adjuvant. Use of liposomes to augment antibody response in the rabbits was successful for the production of anti-BSA antibodies, but failed to result in production of antimoxalactam. One antimoxalactam was chosen for further study, was specifically inhibited with moxalactam (10(-5) mol/L), and did not cross-react with any of the 11 other cephalosporins or eight penicillins tested (in concentrations of 10(-2) mol/L). In addition, the antibody did not demonstrate any carrier specificity. One of eight humans receiving intravenous moxalactam therapy developed a low titer, low avidity antimoxalactam. This patient was a "good responder," inasmuch as he also produced three transfusion-stimulated alloantibodies to red cell antigens during the study. Although the patient developed the antimoxalactam antibody while the drug was being administered, there was no evident adverse clinical reaction. This is the first report of antimoxalactam produced either in experimental animals or in humans. Our data indicate that moxalactam may be a relatively poor immunogen in rabbits requiring special immunization protocols. The one antibody studied does not cross-react with other structurally related antibiotics. Although human antimoxalactam may be produced, no adverse effects were detected in the one case observed.

Animals↗
PubMed1985

Extravascular hemolysis following the administration of cefamandole.

Hemolytic anemia occurred in a 70-year-old female after a five-day course of intravenous cefamandole. The patient's serum contained an IgG antibody which was reactive with red blood cells which had been coated in vitro with cefamandole but not with uncoated cells. An in vitro assay of allogeneic mononuclear phagocytosis of cefamandole-coated red cells sensitized with the patient's anti-cefamandole indicated that the anti-cefamandole could induce significant phagocytosis. The anti-cefamandole was easily inhibited in vitro by cefamandole as well as by a variety of related cephalosporins indicating broad cross-reactivity, with the antigenic site primarily the 7-amino-cephalosporanic acid nucleus. Penicillins could inhibit the anti-cefamandole but only when using concentrations 3-10 X those of cephalosporins. Eleven examples of anti-penicillin tested failed to react with cefamandole-coated red cells. Screening of 344 random sera from hospitalized patients found only five (1.5%) reactive with cefamandole-coated red cells; three of these sera were also reactive with penicillin-coated red cells. The patient's hemolysis subsided following cessation of the drug. This is the first report of anti-cefamandole-induced hemolytic anemia.

Aged↗
PubMed1985

Unmasking of Kx antigen by reduction of disulphide bonds on normal and McLeod red cells.

We have investigated the effect of dithiothreitol (DTT) treatment of human red cells upon the Kx blood group antigen. At low concentrations of DTT (less than or equal to 2 microM) there is enhancement of the Kx antigen concomitant with the complete denaturation of the Jsa and Jsb antigens of the Kell blood system. This unmasking of the Kx antigenic site is near maximal using 2 microM DTT. At this concentration of DTT, only the Jsa and Jsb antigens are completely denatured; all other Kell system antigens tested (K, k, Kpb, Ku) are essentially unaffected. These results argue against the Kx antigen serving strictly as a carbohydrate precursor substance involved in a sequential biosynthetic pathway of Kell blood group antigens. Also, McLeod red cells, after treatment with DTT, were found to contain Kx antigen, although in much lower density than normal red cells, indicating that, although not a typical carbohydrate precursor substance, Kx may, nevertheless, be essential for the serological expression of Kell related antigens. It is hypothesized that the Kx structure and the Kell blood group antigen structure are two separate subunits associated in a quaternary conformation involving at least one interchain S-S bond. Our results should allow for a clearer understanding of the relationship between the serological expression of the Kx antigen and the serologically observed reactivity of the Kell blood group antigens of individuals having normal, Ko and McLeod phenotypes.

Antigens, Bacterial↗