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J L Ambrus

Publications and source records attributed to J L Ambrus.

At least 91 records · Page 5Linked to original sources
PubMed1988

Differential effects of interleukin 2 vs B cell growth factor on human B cells.

The effects of recombinant interleukin 2 (IL-2) and high m.w. (HMW) B cell growth factor (BCGF) were examined on normal human peripheral blood B cells activated with Staphylococcus aureus Cowan I (SAC). When SAC-activated B cells were separated into Tac-antigen (Tac-Ag)+ and Tac-Ag- fractions by a cell sorter, recombinant IL-2 induced only the Tac-Ag+ cells to proliferate, whereas both Tac-Ag+ and Tac-Ag- cells responded to HMW-BCGF (m.w. 60,000). Alternatively, SAC-activated B cells were separated according to density into three fractions: low density (large) cells (82 +/- 15% Tac-Ag+), intermediate density (medium) cells (45 +/- 13% Tac-Ag+), and high density (small) cells (less than 5% Tac-Ag+). Recombinant IL-2 enhanced proliferation of low density cells the most, intermediate density cells less, and high density cells not at all. HMW-BCGF induced all three fractions to proliferate to approximately the same degree. Finally, the effects of IL-2 and BCGF on the DNA and RNA content of the various fractions of B cells was examined. RNA content was greater in IL-2-stimulated B cells than BCGF-stimulated B cells, whereas DNA content was the same in both cell populations. IL-2 and BCGF may preferentially interact with different subpopulations of B cells. The interaction of IL-2 or BCGF with normal activated B cells may induce both similar and different intracellular events.

Adult↗
PubMed1988

A morphological analysis of an in vitro model of cytotoxic antitumor activity.

Models of adoptive immunotherapy and cytotoxicity of lymphocytes isolated from tumor tissues were studied. A microcytotoxicity model utilizing serum-free culture conditions was evaluated by light microscopy, scanning electron microscopy, and transmission electron microscopy for antitumor activity. By examining morphologically the relationship between peripheral blood mononuclear cells and tumor-infiltrating lymphocytes, it was demonstrated that the latter and macrophages had morphological features similar to the cytotoxic cells obtained in vitro from peripheral blood. When allowed sufficient time in our culture conditions, the tumor-infiltrating cytotoxic cells seem to kill the tumor cells within a few days to many months. The ultrastructural morphology of the interaction between the cytotoxic cells and the tumor cells was described as well as some proteinaceous secretory granules that seem to be transferred to the tumor cells through these interactions.

Cell Communication↗
PubMed1988

Studies on the vasoocclusive crisis of sickle cell disease IV. Mechanism of action of pentoxifylline (Trental).

Pentoxifylline was shown to prevent sickling induced by deoxygenation of SS-genotype blood from sickle cell disease patients. It also prevents development of cell stiffness, based on decreased membrane fluidity. This effect is related to increased red cell ATP content, decreased potassium loss during sickling and decreased attachment of hemoglobin to the red cell membrane during sickling. There was no effect on osmotic fragility or mean corpuscular volume. There was some increase in pH of blood from patients in vasoocclusive crisis of sickle cell disease under the effect of pentoxifylline. The consideration is discussed that pentoxifylline may prevent vasoocclusive crisis, but may not abort an existing process.

Adenosine Triphosphate↗
PubMed1988

Ultrastructural descriptions of interactions between tumor-infiltrating lymphocytes and tumor cells in an in vitro model of culture in serum-free medium.

The ultrastructural morphological characteristics of tumor-infiltrating lymphocytes (TIL) and their interactions with tumor cells were studied in a model previously described. In fresh surgical specimens taken from cancer patients, TIL are found in different amounts, in physical contact with tumor cells, without evident cytotoxic activity. As the culture ages in vitro, however, changes appear in the morphology of the TIL along with degenerative changes and eventually death of the tumor cells. The attachments of the TIL to the tumor cells undergo changes as well. During these changes, some proteinaceous material seems to be secreted by the TIL and transferred to the tumor cells. It is inferred that these changes are related to acquisition of cytotoxicity of the TIL, and this possibility is addressed in the discussion. The morphology of the TIL is that of elongated mononuclear cells. They display motility in the culture medium when not attached to tumor cells. Some of these cellular extensions may be quite impressive in their length and tortuosity, and they are described in detail. An attempt is made to speculate on their function as well.

Female↗
PubMed1988

Detailed studies on expression and function of CD19 surface determinant by using B43 monoclonal antibody and the clinical potential of anti-CD19 immunotoxins.

Extensive immunologic surface marker analyses and binding competition assays demonstrated that B43 monoclonal antibody (MoAb) is a new member of the CD19 cluster that recognizes the same surface epitope as several other anti-CD19 MoAbs. We used B43 MoAb to test for CD19 expression on neoplastic cells from 340 leukemia and 151 malignant lymphoma patients and on nonneoplastic cells in normal lymphohematopoietic and nonlymphohematopoietic tissues. Our study more than doubles the total number of cases with classified hematologic malignancies that have been examined for CD19 antigen expression. The data presented confirm that CD19 is the most reliable B lineage surface marker and support our view that this B lineage-restricted surface determinant may be an important functional receptor. Our findings provide unique and direct evidence that (a) CD19 is expressed on leukemic B lineage lymphoid progenitor cells freshly obtained from B lineage acute lymphoblastic leukemia patients but not on normal myeloid, erythroid, megakaryocytic, or multilineage bone marrow progenitor cells; (b) ligation of CD19 with B43 MoAb induces sustained increases in [Ca2+]i when crosslinked and inhibits high-molecular weight B cell growth factor (HMW-BCGF)-induced proliferation of activated B cells without affecting their low-molecular weight B cell growth factor (LMW-BCGF) response; therefore CD19 may be a unique signal receptor; (c) HMW-BCGF and LMW-BCGF augment expression of CD19, which suggests that CD19 and BCGF receptors may be under coordinate regulatory control; (d) approximately two million B43 MoAb molecules per cell can be bound to target B lineage lymphoma cells with a Ka of 1.9 x 10(8)/mol/L; (e) CD19 can undergo B43 MoAb-induced internalization; and (f) the opportunity is thus provided for using anti-CD19 MoAb to deliver toxins to B lineage neoplastic cells for more effective treatment of high-risk leukemia/lymphoma patients.

Antibodies, Monoclonal↗
PubMed1988

Tumor-infiltrating lymphocytes: in vitro characterization of morphological and phenotypical changes.

Mononuclear cells (tumor-infiltrating lymphocytes [TIL]) that invade tumor tissue in fresh surgical specimens were examined and characterized. Such cells were seen in virtually all 52 tumor specimens analyzed and were found to be physically attached to the tumor cells. The morphology of these cells is described with scanning and transmission electron microscopy. Phenotype analysis of these tumor-infiltrating lymphocytes was also performed. In the fresh surgical specimens, while the tumor cells are viable, TIL cells are mostly null cells (except for weak positivity for Leu-1 antigen). As the culture ages in vitro, the TIL phenotype changes drastically to a wide variety of both T and B cells as well as monocyte-macrophage lineage. While these phenotype changes occur, the tumor cells to which the TIL are attached display progressive signs of necrosis and cell death. Tumor cells without attached TIL cells are not affected by necrotic changes. It is speculated that these described changes in the phenotype and morphology of TIL may be related to acquiring cytotoxic activity against the tumor cells. An attempt to control these changes may possibly be useful for clinical application in cancer immunotherapy.

B-Lymphocytes↗
PubMed1987

The role of interleukin 2 in inducing Ig production in a pokeweed mitogen-stimulated mononuclear cell system.

Cyclosporin A (CsA) has been found previously to block mitogen-stimulated T cell proliferation and production of discrete T cell-derived lymphokines such as interleukin 2 (IL 2) and interferon (IFN)-gamma. In addition, CsA blocks pokeweed mitogen (PWM)-driven T cell-dependent differentiation of B cells into immunoglobulin (Ig)-secreting cells. Recently, we reported that CsA (1 microgram/ml) inhibited PWM-induced T cell production of IL 2 and IFN-gamma, but supernatants retained B cell differentiation factor (BCDF)-like activity. The present study demonstrates the ability of CsA to suppress T cell functions in PWM-driven Ig production in mononuclear cells (MNC), and the capacity of exogenous T cell lymphokines to reverse CsA-induced suppression. CsA profoundly suppressed PWM-driven PFC formation (greater than 95%). However, Ig production was substantially reconstituted by the addition of IL 2 at concentrations of 10 to 50 U/ml. In contrast, no effects were observed by the addition of IFN-gamma or BCGF. The kinetics of CsA inhibition of Ig production and IL 2 secretion were found to be closely related. In addition, to obtain effective reconstitution in the CsA-treated PWM-MNC system it was necessary to add IL 2 at the initiation of culture. T cells themselves were also required for B cell differentiation in this system. However, surface Ig+ cells obtained by cell sorting after 3 days of culture could differentiate in the absence of T cells but only in response to IL 2, not in response to IFN-gamma or BCDF. Thus, in PWM-driven B cell differentiation T cells are necessary early in culture, whereas IL 2 is essential from the initial stage of B cell activation through the final stage of B cell differentiation.

Adult↗
PubMed1987

Functional and biochemical characterization of B-cell differentiation factor (BCDF) produced by an HTLV-I-transformed human T-cell clone and demonstration of specific binding of the factor to a BCDF responsive cell line.

We have previously described YA2, a human T-cell clone that secretes B-cell differentiation factor (BCDF) but not B-cell growth factor (BCGF). The BCDFs secreted by YA2 and HTLV-I-transformed YA2 (TYA2) were functionally similar in their ability to stimulate Ig secretion by Staphylococcus aureus Cowan strain I-activated B cells and IgM secretion by SKW6.4 cells. In addition, they were biochemically similar with a MW of 30 kDa by high-performance liquid chromatography (HPLC) sieving, and a pI of 6.0-6.8 by isoelectric focusing. The BCDF activity was not blocked by antibodies to interleukin 2 and BCGF. BCDF was purified from TYA2 supernatant by sequential media protein immunoadsorption, flat bed isoelectric focusing, HPLC TSK 2000 sieving, and repeated immunoadsorption and was then iodinated. The iodinated material had functional BCDF activity and migrated to a single band at MW 30 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and at pI of 6.8 by polyacrylamide gel isoelectric focusing. 125I-BCDF purified in this manner bound specifically to a BCDF-responsive cell line and not to phytohemagglutinin-activated T cells. 125I binding to the BCDF-responsive cell line was competitively inhibitable by the addition of cold BCDF. Thus we have purified and characterized a factor with BCDF activity and demonstrated that this factor binds specifically to a BCDF-responsive cell line.

Antibody Formation↗
PubMed1987

Elevation of serum IgG levels and normalization of T4/T8 ratio after hepatitis in a patient with common variable hypogammaglobulinemia.

Acute hepatitis infection developed in a 47-year-old male patient with common variable hypogammaglobulinemia as a consequence of plasma transfusion therapy. Coincident with increases in serum transaminase activities indicative of acute hepatitis, serum IgG levels continued to rise to 506 mg/dl. When plasma replacement therapy was stopped, a transient decline in IgG level (to 371 mg/dl) was produced, followed by a sharp increase in IgG to 607 mg/dl. During this period, the patient's T4/T8 ratio, which had been inverted (0.89), exhibited significant normalization to 1.57. Nevertheless, the patient failed to produce specific antibody after immunization with a number of defined antigens. The mechanism whereby this presumed non-A, non-B hepatitis augmented endogenous IgG production in this patient remains unknown but may be related to diminished suppressor T cell activity. The patient's inability to produce specific antibody during this period suggests an underlying defect in one or more lymphocyte subsets involved in either helper T cell activity and/or immunologic memory.

Agammaglobulinemia↗
PubMed1987

Treatment of complications of peripheral obstructive arterial disease with prostaglandin E1.

Forty-one subjects diagnosed with complications of peripheral obstructive arterial disease were treated with continuous infusions of Prostaglandin E1 (PGE1) over a three-week period during 1981-1982 in an open-label, uncontrolled study under ward conditions. Ischemic rest pain and ulcers were treated with intravenous infusions of PGE1 at dose rates of 14-21 ng kg-1 min-1 for seventy hours, once a week. Symptomatic relief of rest pain and spontaneous healing of stable ulcers occurred. Whereas classically dependable noninvasive circulation evaluations were not prognostic of the treatment's success, they did suggest local and rheological changes rather than a generalized vasodilation. The PGE1 infusion is efficacious for an unknown length of time, which may somehow be related to inhibition of platelet aggregation. Since transient ischemic attack (TIA) and cerebrovascular accident (CVA) were found to be associated with PGE1 infusion, cerebrovascular evaluation must be conducted prior to considering PGE1 replacement therapy for the individual patient.

Aged↗
PubMed1987

Extracorporeal enzyme reactors for depletion of phenylalanine in phenylketonuria.

Multitubular enzyme reactors with immobilized enzymes were developed to achieve depletion of circulating substrate by extracorporeal means. To act as prototypes, reactors were prepared with immobilized L-phenylalanine ammonia-lyase, an enzyme that metabolizes phenylalanine to trans-cinnamic acid and ammonia without the need for a coenzyme. We report the first application of phenylalanine ammonia-lyase reactors in an extracorporeal circulation system in a patient with phenylketonuria. A phenylalanine level of 1.82 mmol/L (for the last 6 years) decreased to 1.24 mmol/L after 5.5. hours of treatment, without the enzyme entering the circulation. Total phenylalanine depletion from blood and tissue stores was estimated at 1800 mg. The hemodialysis-like procedure proved to be without side effects, specific for phenylalanine, and suitable in the management of pregnant women with phenylketonuria and late-onset hyperphenylalaninemia. The extracorporeal use of enzyme reactors for temporary enzyme replacement represents a new, safe, and effective therapeutic modality.

Adult↗
PubMed1987

Medical education.

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Education, Medical↗
PubMed1987

Studies on the vasoocclusive crisis of sickle cell disease. III. In vitro and in vivo effect of the pyrimido-pyrimidine derivative, RA-233: studies on its mechanism of action.

Red cell deformability was found to be impaired in SS- and SC-genotype and to a lesser extent SA-genotype red blood cells as compared with those of AA-genotype. RA-233 in vitro improved deformability according to a bell-shaped dose-response curve. RA-233 also prevented experimental vasoocclusive crisis in Macaca arctoides. Deoxygenation of SS-genotype red cells resulted in sickle shape transformation, ATP depletion, potassium efflux, and attachment of hemoglobin molecules to the membrane. These changes were prevented by RA-233. Suspending SS-genotype red blood cells in potassium rich tris-buffer also prevented potassium efflux during deoxygenation and also decreased cellular deformability. RA-233 had no effect on osmotic fragility of SS-genotype red blood cells.

Adult↗