PubMed Health⌕ Search

Biomedical subjects

C L Berger

Publications and source records attributed to C L Berger.

At least 19 recordsLinked to original sources
PubMed1991

Inhibition of antiskin allograft immunity induced by infusions with photoinactivated effector T lymphocytes (PET cells). Is in vivo cell transferrable?

We previously reported producing donor-specific tolerance to alloantigens by intravenous exposure to pretreated antidonor T cells. The current study extends that work by adoptively transferring the donor-specific tolerance into naive syngeneic recipients. Eight days after BALB/c mice received histoincompatible CBA/j skin grafts, their splenocytes which included an expanded population of cells mediating rejection were treated with 100 ng/ml 8-methoxypsoralen (8-MOP) photoactivated by 1 Joule/cm2 of ultraviolet A (UVA) light prior to infusion into naive BALB/c recipients. Whereas 8-MOP itself is biologically inert, photoactivated 8-MOP crosslinks DNA by covalently binding to pyrimidine bases. Recipient BALB/c mice which had been previously demonstrated to be hyporesponsive to CBA/j alloantigens in mixed leukocyte culture (MLC), cytotoxicity (CTL) and in vivo delayed type hypersensitivity (DTH) assays were the donors of spleen cells for the adoptive transfer experiments. Fifty to one hundred million viable spleen cells from these pretreated BALB/c mice were transferred into naive syngeneic recipients which then were tested for DTH response and allograft survival to the relevant and irrelevant antigens. The radiosensitivity of this transferrable suppression was evaluated by exposing the adoptively transferred cell population to 3200 rads of C-irradiation prior to cell transfer. The phenotype of the cells transferring this suppressive response was performed by depleting specific populations of cells with monoclonal antibodies prior to cell transfer. In vivo the DTH response of the pretreated BALB/c mice was specifically suppressed to the relevant alloantigen, correlating with retention of CBA/j skin grafts for up to 42 days post engraftment without visual evidence of rejection, in comparison to control mice complete rejection of the skin graft in less than 8 days. In vitro, splenocytes from BALB/c recipients of pretreated syngeneic splenocytes containing large numbers of BALB/c anti-CBA/j T cells proliferated less in MLC and generated lower cytotoxic T cell responses to CBA/j alloantigens than did controls and suppressed the naive and sensitized BALB/c MLC and CTL responses to CBA/j alloantigen. This specific suppressive response to alloantigen was optimally transferred into syngeneic naive recipients when the adoptive transfer was performed on the sixth day after the last infusion received by the spleen cell donor mice. The adoptive transfer of this suppressive response was abrogated by the prior X-irradiation of the donor spleen cells and significantly abolished by the depletion of Thy-1+, Lyt-2+, L3T4- T lymphocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Antigen-specific tolerance induced by autoimmunization with photoinactivated syngeneic effector cells.

Development of a protocol that could invoke specific suppression of an undesired immune response, while sparing normal immune competence, would be of great clinical value. This report demonstrates that multiple infusions of splenocytes sensitized in vivo to sheep red blood cells (SRBC) and photoinactivated in vitro with 8-methoxypsoralen and ultraviolet A light can render a syngeneic recipient selectively unresponsive to subsequent challenge with this antigen. Mice treated in this fashion did not develop a T cell-mediated delayed type hypersensitivity (DTH) reaction to SRBC. In contrast, control mice exposed to nonimmune splenocytes pretreated in an identical manner developed a normal DTH response to SRBC, thereby demonstrating that drug and light in the absence of effector T cells were not suppressive. Inhibition of the DTH response was antigen specific, since animals rendered unresponsive to SRBC developed a normal DTH response to chicken red blood cells. Cell transfer experiments demonstrated that unprimed recipients of splenocytes from mice rendered unresponsive to SRBC could not mount a DTH reaction when challenged. Moreover, this procedure can also suppress established immunity to that antigen. The use of photoinactivated syngeneic antigen-reactive effector cells as immunosuppression agents suggests that this method may be clinically useful in inhibiting pathogenic antigen-specific immunologic reactions.

Animals↗
PubMed1991

Autoregulation of the immune response in autoimmune disease and cardiac transplantation by photoinactivated autologous lymphocytes.

These studies demonstrate that photochemotherapy can be successfully evaluated in animal models. The therapy mediates specific suppression of immune responses and appears to operate at the level of the effector T cells. Future studies will focus on isolation and characterization of the host response to photochemotherapy. The extention of this form of therapy to conditions mediated by dysfunctional regulation of effector T cells is already in progress in clinical trials of cardiac allograft transplantation and autoimmune disease. The results of these trials will provide more evidence on the role of this form of therapy in autoregulation of the immune response.

Animals↗
PubMed1991

Rotational dynamics of actin-bound intermediates in the myosin ATPase cycle.

We have used saturation-transfer electron paramagnetic resonance (ST-EPR) to detect the microsecond rotational motions of spin-labeled myosin subfragment one (MSL-S1) bound to actin in the presence of the ATP analogues AMPPNP (5'-adenylylimido diphosphate) and ATP gamma S [adenosine 5'-O-(3-thiotriphosphate)], which are believed to trap myosin in strongly and weakly bound intermediate states of the actomyosin ATPase cycle, respectively. Sedimentation binding measurements were used to determine the fraction of myosin heads bound to actin under ST-EPR conditions and the fraction of heads containing bound nucleotide. ST-EPR spectra were then corrected to obtain the spectrum corresponding to the ternary complex (actin.MSL-S1.nucleotide). The ST-EPR spectrum of MSL-S1.AMPPNP bound to actin is identical to that obtained in the absence of nucleotide (rigor complex), indicating no rotational motion of MSL-S1 relative to actin on the microsecond time scale. However, MSL-S1-ATP gamma S bound to actin is rotationally mobile, with an effective rotational correlation time (tau r) of 17 +/- 2 microseconds. This motion is similar to that observed previously for actin-bound MSL-S1 during the steady-state hydrolysis of ATP [Berger et al. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 8753-8757]. We conclude that, in solution, the weakly bound actin-attached states of the myosin ATPase cycle undergo microsecond rotational motions, while the strongly bound intermediates do not, and that these motions are likely to be involved in the molecular mechanism of muscle contraction.

Actins↗
PubMed1991

Binding of preformed xenoantibodies to porcine bioprosthetic valves.

We have investigated whether preformed antibodies against xenoantigens bind to cellular elements remaining on porcine bioprosthetic valves after various methods of preservation. Fresh porcine valves treated with either acetone, 4% formaldehyde, or 0.625% glutaraldehyde, as well as an unfixed valve, were incubated with antiserum against porcine xenoantigens. This serum was prepared using the affinity purification method with porcine lymphocytes as the target. The valves were stained with secondary fluorescein-conjugated antibody against immunoglobulin M or immunoglobulin G and examined under fluorescent microscopy. Intense binding of immunoglobulin M to the endocardium was observed in the unfixed valve as well as in valves fixed in acetone and formaldehyde. Glutaraldehyde fixation eliminated binding of antibody. Binding was not noted within the connective tissue. No binding of antiimmunoglobulin G was noted on the endocardium of any of the sections. Examination of three glutaraldehyde-treated porcine valves explanted from the aortic position after 10 years in situ showed no immunoglobulin deposition. These results demonstrate the elimination of antigenicity to preformed antibodies in the endocardium and connective tissue of glutaraldehyde-preserved porcine valves. The findings may, in part, explain the poor performance of formaldehyde-preserved bioprosthetic xenograft valves in the past and support the use of glutaraldehyde as a preferred agent for preservation of bioprosthetic endovascular materials.

Animals↗
PubMed1991

Inhibition of anti-skin allograft immunity induced by infusions with photoinactivated effector T lymphocytes--the congenic model.

We have previously reported the capacity to produce donor-specific tolerance to alloantigens by intravenous exposure to pretreated antidonor T cells. The current study has refined this system by using congenic mice differing only at the H-2 major histocompatibility complex genetic loci. Twelve days after B10 mice received MHC-incompatible B10.D2 skin grafts, their splenocytes that included an expanded population of cells mediating rejection were treated with 100 ng/ml 8-methoxypsoralen (8-MOP) photoactivated by 1 J/cm2 of ultraviolet A prior to infusion into naive B10 recipients. Whereas 8-MOP itself is biologically inert, photoactivated 8-MOP crosslinks DNA by covalently binding to pyrimidine bases. Recipient B10 mice were tested for tolerance to B10.D2 alloantigens in mixed leukocyte culture (MLC), cytotoxicity (CTL), and to in vivo delayed type hypersensitivity assays and challenged with a fresh B10.D2 graft. In vivo, the DTH response of the pretreated B10 mice was specifically suppressed to the relevant alloantigen, correlating with retention of B10.D2 skin grafts for up to 22 days postengraftment without visual evidence of rejection, in comparison to control complete rejection of the skin graft in less than 12 days. In vitro, splenocytes from B10 recipients of pretreated syngeneic splenocytes containing large numbers of B10 anti-B10.D2 T cells proliferated less in MLC and generated lower cytotoxic T cell responses to B10.D2 alloantigens than did controls and suppressed the B10 MLC and CTL responses to B10.D2 alloantigen. These results reveal that, in a highly defined congenic transplantation system, infusions of photoinactivated effector cells resulted in selective inhibition of the in vivo responses that correlated with allograft rejection and permitted prolonged retention of histoincompatible skin grafts. This approach may have significant practical applicability for treatment of human disorders caused by aberrant T cells.

Animals↗
PubMed1990

Inhibition of autoimmune disease in a murine model of systemic lupus erythematosus induced by exposure to syngeneic photoinactivated lymphocytes.

MRL/l mice develop progressive, virulent autoimmune disease that has many of the features of systemic lupus erythematosus. Prophylactic treatment of MRL/l mice with syngeneic photoinactivated autoimmune splenocytes improves survival and inhibits the fulminant hyperproliferation of abnormal T cells and the production of high titer anti-DNA antibody invariably found in untreated mice. The proliferation of Thy 1+ splenic T cells was significantly decreased, and prolonged retention of the response to T-cell mitogen was found in treated mice. Treatment with unmodified cells induced a partial inhibition of disease features which did not prolong survival rates. These results suggest that phototherapy potentiates a normal immunoregulatory process which enables suppression of the development of abnormal cell populations in young MRL/l mice with relatively intact immune systems.

Animals↗
PubMed1990

BE-2 antigen: appearance in activation and long-term growth of T cells.

The BE-2 lymphocyte surface protein is frequently expressed by the malignant cells of cutaneous T-cell lymphoma (CTCL) but is not detectable on the surface of normal resting peripheral blood lymphocytes. The expression of BE-2 by normal T cells can be induced by lectin stimulation. Membrane expression of BE-2 surpasses that of the membrane receptor for IL-2, another T-cell activation marker, at day 5. The peak expression of BE-2 appears at day 6-8. The appearance of BE-2 could also be demonstrated after anti-CD3 and allogeneic stimulation. Long-term T-cell clones derived from normal donors and maintained in culture with periodic stimulation were also found to express BE-2 continuously. Thus, BE-2 is a late activation marker not expressed on normal peripheral blood lymphocytes and pathologically expressed on circulating malignant cells in the disease CTCL.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

Photolysis of a photolabile precursor of ATP (caged ATP) induces microsecond rotational motions of myosin heads bound to actin.

To test the proposal that ATPase activity is coupled to the rotation of muscle cross-bridges (myosin heads attached to actin), we have used saturation-transfer EPR to detect the rotational motion of spin-labeled myosin heads (subfragment 1; S1) bound to actin following the photolysis of caged ATP (a photoactivatable analog of ATP). In order to ensure that most of the heads were bound to actin in the presence of ATP, solutions contained high (200 microns) actin concentrations and were of low (36 mM) ionic strength. Sedimentation measurements indicated that 52 +/- 2% of the spin-labeled heads were attached in the steady state of ATP hydrolysis during EPR measurements. Five millimolar caged ATP was added to the actin-S1 solution in an EPR cell in the dark, with no effect on the intense saturation-transfer EPR signal, implying a rigid actin-S1 complex. A laser pulse produced 1 mM ATP, which decreased the signal rapidly to a brief steady-state level that indicated only slightly less rotational mobility than that of free heads. After correcting for the fraction of free heads, we conclude that the bound heads have an effective rotational correlation time of 1.0 +/- 0.3 microseconds, which is about 100 times shorter (faster) than that in the absence of ATP. To our knowledge, this is the first direct evidence that myosin heads undergo rotational motion when bound to actin during the ATPase cycle. It is likely that similar cross-bridge rotations occur during muscle contraction.

Actins↗
PubMed1989

Primate cardiac allo-and xenotransplantation: modulation of the immune response with photochemotherapy.

Survival of heterotopic allo- and xenografts was studied in a primate cardiac transplantation model. Initially, animals were presensitized to donor xenoantigens by blood transfusion and treated with strategies designed to elicit pretransplant immunosuppression. These animals underwent rapid rejection whether treated with ciclosporin and conventional immunosuppression, autologous sera, sensitized lymphocytes, or photochemotherapy. In a nonsensitized xenograft study, xenografts were maintained for prolonged periods with a combination of ciclosporin and photochemotherapy. All animals treated with photochemotherapy demonstrated periodic suppression of the mixed leukocyte culture response to their donor. Inhibition of lymphocytotoxic antibody was achieved only in animals treated with both ciclosporin and photochemotherapy. Xenosensitized animals were secondarily exposed to donor alloantigens. These animals were successfully allografted. Ciclosporin therapy was terminated and the animals maintained by photochemotherapy alone. This preliminary trial indicates that a combination of ciclosporin and photochemotherapy may be of value in maintaining concordant xenografts and preventing antibody mediated rejection.

Animals↗
PubMed1988

Dual genotype in cutaneous T cell lymphoma: immunoglobulin gene rearrangement in clonal T cell malignancy.

Genomic DNA digests of peripheral blood lymphocytes from 13 patients with the leukemic phase of the T cell neoplasm cutaneous T cell lymphoma were studied by hydridization using probes for the constant region of the beta chain of the T cell receptor, the joining region of the immunoglobulin heavy chain gene, and the kappa and lambda light chain genes. Lymphocytes from all 13 cutaneous T cell lymphoma patients contained DNA with clonal rearrangements of the beta chain gene of the T cell receptor. In addition, DNA from 4 patients contained an immunoglobulin gene rearrangement. T cell enrichment studies of peripheral blood lymphocytes from 2 patients confirmed that the immunoglobulin gene joining region rearrangement was confined to the T cell population. These results demonstrate that cutaneous T cell lymphoma is a clonal T cell malignancy that frequently expresses a dual genotype. A multiparameter approach, including DNA probes for the beta chain of the T cell receptor, as well as the immunoglobulin genes, immunophenotyping, and cytogenetics, is valuable in the diagnosis of cutaneous T cell lymphoma.

Antibodies, Monoclonal↗
PubMed1987

Clonal chromosomal abnormalities in cutaneous T-cell lymphoma.

Chromosome analysis from stimulated and unstimulated lymphocytes of blood, skin, and lymph nodes demonstrated a clonal chromosomal abnormality in eight of 46 patients with cutaneous T-cell lymphoma (CTCL). Nonclonal abnormalities were found in nine other patients. Unstimulated lymph node cultures identified the highest proportion of clonal changes. Clonal changes were found most often in patients with advanced disease, and in patients who tested positive with a monoclonal antibody previously shown to detect the T-cells involved in CTCL. Analysis of the eight abnormal clones and seven others found before or since this consecutive series showed that identifiable changes involving the known sites of T-cell receptor genes on chromosomes #7 and #14 were not usually present. An association between CTCL and chromosome rearrangements of chromosome #10 is suggested both from our cases and those found in the literature. This observation is of interest because this chromosome contains the gene for the interleukin-2 receptor.

Adult↗
PubMed1987

Clinical evolution of cutaneous T cell lymphoma in a patient with antibodies to human T-lymphotropic virus type I.

A woman who emigrated to the United States from the Dominican Republic developed the first signs of cutaneous T cell lymphoma during the last trimester of her pregnancy. This patient, found to have a positive reaction against human T-lymphotropic (leukemia-lymphoma) virus type I (HTLV-I), was followed up prospectively from the appearance of the initial skin lesion to the development of high-count helper T cell leukemia. Antibodies reactive with the core protein of HTLV-I were also identified in her husband and mother but not in her 2-year-old daughter. Examination of the patient's course provides clues about the latency period and transmission of HTLV-I and highlights similarities between HTLV-I-positive and HTLV-I-negative cutaneous T cell lymphoma.

Adult↗
PubMed1986

Tumor-associated antigen is expressed on lymphocytes from patients with acquired immunodeficiency syndrome.

Monoclonal antibody BE2 recognizes an antigen found on malignant T4+ lymphocytes from cutaneous T-cell lymphoma patients (CTCL). Normal peripheral blood lymphocytes do not express detectable levels of BE2 antigen. Forty-eight percent of patients with the acquired immunodeficiency syndrome (AIDS) had lymphocyte populations that were reactive with monoclonal antibody BE2. Peripheral blood lymphocytes from healthy homosexuals, patients with classical Kaposi's sarcoma or viral syndromes, and healthy normal controls were BE2-. Double-labeling studies demonstrated that BE2+ cells were T lymphocytes. This observation demonstrates that some AIDS patients as well as CTCL patients have circulating cells that express a common lymphocyte abnormality.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Phorbol esters increase calcitonin gene transcription and decrease c-myc mRNA levels in cultured human medullary thyroid carcinoma.

Medullary thyroid carcinoma is a tumor of the calcitonin-secreting thyroid C-cell, with a variable malignant potential. Virulent tumors are characterized by decreased calcitonin production, suggesting the emergence of a less differentiated medullary thyroid carcinoma cell. In order to further delineate relationships between tumor progression and status of differentiation of medullary thyroid carcinoma cells, we have sought to chemically manipulate the TT cell line, an established culture of human medullary thyroid carcinoma, derived from a patient with aggressive disease. We found that the phorbol esters, 12-O-tetradecanoyl phorbol 13-acetate and phorbol 12,13-dibutyrate 1) altered the morphology of the TT cells towards that of high-calcitonin-containing cells; 2) enhanced calcitonin secretion 7-fold; 3) increased calcitonin production at the transcriptional level by 2-fold; 4) inhibited cellular proliferation; and 5) decreased, by 80%, the levels of the c-myc gene mRNA. These data suggest that phorbol esters induce, in human medullary thyroid carcinoma cells in culture, a programmed pattern of events resulting in differentiation of these cells.

Calcitonin↗