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M J Bozdech

Publications and source records attributed to M J Bozdech.

At least 19 recordsLinked to original sources
PubMed1987

Differences in nonspecific esterase from normal and leukemic monocytes.

Nonspecific esterase (NSE) is used to identify normal and leukemic mononuclear phagocytes cytochemically. It can be demonstrated by the hydrolysis of alpha-naphthyl acetate or butyrate. NSE from leukapheresed leukemic monocytes were extracted with several types of detergent and grouped into two isoelectric point (pl) categories based on the ease of solubility: pl 5.7-6.3 (8 bands) greater than or equal to pl 6.6-7.6 (6 bands). Normal monocytes yielded only the pl 5.7-6.3 isozymes. Isozymes from both leukemic and normal monocytes were inhibited similarly by sodium fluoride, pH less than 4.7, and a serine active site inhibitor. All isozymes were bound by Sepharose-concanavalin A (Con-A) and displayed similar substrate preferences and pH v activity slopes. Under the conditions of detergent solubilization, the smallest mol wt species retaining enzymatic activity was 50 +/- 5 kd. Despite these similarities, the isozymes of pl 5.7 through 6.3 and pl greater than 6.3 exhibited different degrees or types of inhibition by phenylmethylsulfonyl fluoride (PMSF), resistance to heat and antigenic character. Thus, the esterase isozymes represent two families of glycoproteins, both of them probable cell surface enzymes, resembling classical liver carboxyl or B-esterases (EC 3.1.1 1).

Carboxylesterase↗
PubMed1985

Relapse of host leukemic lymphoblasts following engraftment by an HLA-mismatched marrow transplant: mechanisms of escape from the "graft versus leukemia" effect.

Leukemic relapses and graft versus host disease (GvHD) remain major complications following allogeneic bone marrow transplantation for leukemia. We present clinical and laboratory details for an eight-year-old boy who received a T-cell-depleted HLA-mismatched marrow transplant as therapy for acute lymphoblastic leukemia (ALL) in second remission. Engraftment with donor marrow was prompt and without any acute GvHD. Nevertheless, the patient's original ALL recurred and proved fatal. The patient remained a chimera with persistent donor lymphocytes present at the time of posttransplant relapse and subsequent to treatment with unsuccessful reinduction chemotherapy. In vitro immune studies showed that these leukemic cells could be recognized and destroyed by the donor's lymphocytes. The relapse itself suggests, however, that the donor's lymphocytes did not effectively destroy the patient's histoincompatible ALL cells in vivo following establishment of the chimeric state. Potential mechanisms are presented to account for this presumed "escape" from the postulated "graft versus leukemia" effect.

Acute Disease↗
PubMed1985

Clinical trial depleting T lymphocytes from donor marrow for matched and mismatched allogeneic bone marrow transplants.

Nine patients received T-lymphocyte-depleted histocompatible bone marrow and 28 patients received T-lymphocyte-depleted histoincompatible bone marrow. Eight of nine patients receiving matched bone marrow quickly engrafted without severe graft-versus-host disease (GvHD). None of the eight patients received anti-GvHD prophylaxis medications. Two of these eight patients are currently alive. Nonengraftment and severe GvHD were problems seen in some of the patients given the histoincompatible bone marrow. Additional cytarabine pretransplant permitted engraftment in those patients undergoing histoincompatible transplants for treatment of malignancy, and prednisone and cyclosporine posttransplant reduced the incidence of acute GvHD in those given T-lymphocyte-depleted grafts. Seven of these 28 patients are currently alive. T-lymphocyte-depleted marrow can reduce the occurrence or prevent severe acute GvHD, especially when combined with additional prednisone and cyclosporine; however, the impact on relapse patterns and survival remains to be determined. The occurrence of nonengraftment and treatment-related lymphomas are formidable problems to overcome.

Adolescent↗
PubMed1985

Transplantation of HLA-haploidentical T-cell-depleted marrow for leukemia: addition of cytosine arabinoside to the pretransplant conditioning prevents rejection.

A total of 41 patients with hematologic malignancies (other than acute leukemia in relapse) received allogeneic bone marrow transplants at the University of Wisconsin from 1 April 1980 through 31 March 1984. In an effort to minimize graft-versus-host disease, marrow was depleted of T-lymphocytes in vitro with monoclonal anti-T-cell antibody and complement prior to infusion for seven of 19 recipients of marrow from HLA-identical, MLC-nonreactive siblings, and for all 22 recipients of marrow from MLC-reactive HLA-haploidentical donors. The recipients of HLA-identical T-depleted marrow all showed excellent engraftment following standard pre-BMT conditioning with cyclophosphamide and total body irradiation. In contrast, five of five recipients of T-depleted haploidentical marrow failed to engraft following this same conditioning regimen. The addition of cytosine arabinoside to the pretransplant conditioning appeared to correct this problem, allowing engraftment in 14 of 17 subsequent patients. These clinical results, coupled with prior in vitro data, demonstrate the need to adequately suppress residual host-versus-graft immunity in order to prevent the rejection of T-cell-depleted HLA-haploidentical bone marrow.

Adolescent↗
PubMed1984

Late recurrences of histiocytic lymphoma after treatment.

Disease-free intervals of 2 to 3 years after treatment of histiocytic lymphoma are generally thought to represent cures; flat survival curves beyond 3 years in several studies support this notion. Four case reports of histiocytic lymphoma recurrences 25, 10, 9 and 6 years, respectively, after the initial diagnosis are presented. Histologic confirmation comparing primary and recurrent disease is presented. The potential biological significance of such patient reports is discussed.

Adult↗
PubMed1984

The in vivo distribution of indium-111 labeled in vitro alloactivated syngeneic lymphocytes in a patient with relapsed acute myelomonocytic leukemia: implications for adoptive chemoimmunotherapy.

A single patient who had a leukemic relapse six months after receiving a syngeneic bone marrow transplant was given "adoptive chemoimmunotherapy." Lymphocytes from the patients identical twin were alloactivated and grown in T cell growth factor in vitro. After receiving chemotherapy to reduce the number of relapsed leukemia cells, he received 1.1 X 10(10) in vitro alloactivated twin lymphocytes via intravenous and intraperitoneal injections. Although progressive Candidal pneumonia was fatal and prevented analysis of either efficacy or delayed toxicity of this potential form of therapy for this patient, radioactive 111In labelling and scanning showed dissemination of these lymphocytes following either injection route, with no clinical evidence of immediate toxicity.

Adult↗
PubMed1983

HLA identical leukemia cells and T cell growth factor activate cytotoxic T cell recognition of minor locus histocompatibility antigens in vitro.

Lymphocytes from a healthy HLA-identical bone marrow transplant donor were tested for their ability to destroy her brother's acute myelogenous leukemia blasts in vitro. Primary mixed lymphocyte culture (MLC) and cell-mediated lysis (CML) responses between the patient's remission (pretransplant) and donor's lymphocytes were negative. Stimulation of donor lymphocytes for 7 d in vitro with irradiated leukemia cells, leukemia cells plus allogeneic irradiated lymphocytes, or a pool of irradiated lymphocytes from 10 donors, did not activate any cytotoxic cells able to destroy the HLA identical leukemic blasts. Further culturing for 7 additional d in T cell growth factor (TCGF) generated lymphocytes that induced effective cytotoxicity against the leukemic blasts, but not against autologous lymphocytes. Effective killing against the leukemia was observed only in cultures initially stimulated with the irradiated leukemia cells. These cytotoxic cells were maintained in TCGF and mediated persistent killing against the leukemic target cells. They were also able to destroy lymphocytes from the patient's mother and father, but not from an unrelated cell donor. This suggested specific recognition of non-HLA antigens inherited by the patient, that were foreign to the HLA identical bone marrow donor. These lymphocytes were cloned by a limiting dilution technique and one clone maintained cytotoxicity to the AML blasts and the father's lymphocytes, but not lymphocytes from the mother or an HLA-identical donor. This cytotoxicity was inhibited by a monoclonal anti-HLA antibody. Thus, in vitro sensitization of this sibling's lymphocytes with AML blasts followed by TCGF expansion, and cloning, enabled the detection of HLA-restricted cytotoxic cells that recognize minor locus histocompatibility antigens. This immune recognition may be relevant to the "graft vs. leukemia" effect that has been observed in leukemic animals and patients following histocompatible hematopoietic transplants.

Adult↗
PubMed1983

Pediatric bone marrow transplantation: current progress and future prospects.

Ongoing clinical and laboratory research is being directed at the many problems and complications associated with clinical bone marrow transplantation. The most important goals are to increase the long-term survival of patients receiving bone marrow transplants, decrease the morbidity associated with the process, and extend this therapeutic modality to patients in need of a transplant, but without an HLA identical sibling. In addition, as these problems are resolved, and the toxicity of BMT is controlled, this form of therapy may become the treatment of choice for a number of inherited and acquired hematologic, immunologic, and metabolic disorders that are chronically progressive but ultimately fatal, yet are not now routinely treated with BMT due to the acute morbidity and mortality associated with this major procedure.

Bone Marrow Transplantation↗
PubMed1981

Identification of alpha-naphthyl butyrate esterase as a plasma membrane ectoenzyme of monocytes and as a discrete intracellular membrane-bounded organelle in lymphocytes.

A reaction for an esterase, with a nonhalogenated, short-chain naphthyl ester (alpha-naphthyl butyrate or alpha-naphthyl acetate) as the substrate, has been used to identify mononuclear phagocytes by light microscopy. By analyzing techniques used in the collection, separation, fixation, processing, and embedding of human blood leukocytes for electron microscopy, we adapted the light microscopic method for use in determining the fine structural localization of this reaction. In monocytes, the reaction product covered the external surface of the plasma membrane. This distribution indicated that monocytic esterase is an ectoenzyme. The addition of NaF completely inhibited the monocytic reaction. In lymphocytes, the reaction product was localized in membrane-bounded intracellular organelles, similar to those previously shown to contain phospholipid and called Gall bodies. These organelles correspond with the punctate densities or focal reaction product observed by light microscopy. Other investigators believe that this distribution of enzyme in lymphocytes marks a subset of T cells, the Tmicro. The lymphocytic reaction was not inhibited by NaF.

Carboxylic Ester Hydrolases↗
PubMed1981

Hypokalemia in nonblastic chronic myelogenous leukemia.

Hypokalemia has been noted as a frequent complication of acute leukemia. To our knowledge, an association of this electrolyte disturbance with chronic myelogenous leukemia (CML), not in blast crisis, has never been reported. We report a unique case of hypokalemia that complicated the clinical course of a patient with nonblastic CML. The pathogenesis of the hypokalemia was shown to be inappropriate hyperkaluresis, which appeared to be related to lysozymuria and a large tumor burden. We discuss the pathogenesis of hypokalemia in leukemia. We think that the unusual features associated with CML in this case make a large tumor burden their most likely underlying cause. This may help explain the still confusing and unresolved relationship between lysozymuria and potassium wasting in leukemia.

Humans↗
PubMed1980

Partial peroxidase deficiency in neutrophils and eosinophils associated with neurologic disease. Histochemical, cytochemical and biochemical studies.

Partial peroxidase deficiency was discovered by means of automated continuous-flow cytochemistry (Hemalog D) in the neutrophils and eosinophils of a patient admitted for evaluation of the gradual onset of intellectual deterioration. Wright's stain and routine benzidine peroxidase reaction on peripheral blood smears showed a normal differential count and peroxidase activity, respectively, but smears stained for peroxidase using 4-chloro-1-naphthol, the reagent used in Hemalog D, showed absence of enzymatic activity in neutrophils and eosinophils. Electron microscopy using the Graham-Karnovsky diamino-benzidine method confirmed these findings, demonstrating a new pattern of peroxidase deficiency in which a decreased number of peroxidase-positive granules were found in all neutrophils and, surprisingly, also in eosinophils. Bio-chemical studies also showed that the apparent deficiency is due to an abnormal proportion of "insoluble" peroxidase. These results and the clinical findings for the patient are consistent with the diagnosis of ceroid lipofuscinosis (Kuf's disease).

Bone Marrow↗
PubMed1978

Doxorubicin cardiotoxicity. Serial endomyocardial biopsies and systolic time intervals.

Doxorubicin, whose dose-limiting toxicity is cardiomyopathy, was given to four cancer patients. Endomyocardial biopsy specimens and test results of cardiac function were obtained before, during, and after treatment. The biopsy specimens were examined by light and electron microscopy and were graded blindly. Evidence of specific doxorubicin injury was found in 3/4 patients with as little as 180 mg/sq m of the drug and became progressively more severe with higher doses. All test results of cardiac function, including systolic time intervals, remained normal. These data suggest that a specific, progressive subclinical injury to the heart occurs with doxorubicin therapy, which cannot be reliably detected by routine tests. This potential risk must be taken into account with the use of doxorubicin, especially when combined with synergistic agents.

Adult↗
PubMed1977

Platelet-latelet-.

Two patients with thrombotic thrombocytopenic purpura were seen. Aspirin, dipyridamole, and sulfinpyrazone were administered to patient 1 after splenectomy, and administration of high-dose prednisone and methylprednisolone failed to induce remission. The platelet count rose, but the patient had a relapse when the dipyridamole dose was tapered. This condition responded to an increase of the drug, and the patient obtained a long-lasting remission. A splenectomy was not performed on patient 2, and all three platelet-inhibiting drugs, together with prednisone, were given. This resulted in a prompt remission that has been sustained for 29 weeks. Morphologic changes in the peripheral blood smear remained for several weeks after other features of the disease had resolved. Thus, in both cases, platelet-inhibiting drugs appeared to induce a remission.

Adult↗