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Biomedical subjects

C L Berger

Publications and source records attributed to C L Berger.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1984

Monoclonal antibody 4F2 reactive with basal layer keratinocytes: studies in the normal and a hyperproliferative state.

To establish a method for separating different keratinocyte subpopulations in the epidermis, we studied the specificity of monoclonal antibody 4F2 for keratinocytes. Preliminary screening experiments had previously demonstrated 4F2 reactivity with the epidermis. 4F2 reacted with a subpopulation (19.29 +/- 5.23%) of human epidermal cells in suspension. The membrane antigen identified by 4F2 continues to be expressed by cultured keratinocytes. In frozen tissue section using an indirect immunofluorescence technique, the 4F2-positive cells in the basal layer are sharply demarcated from the negative suprabasilar layers. Even in the hyperproliferative state of psoriasis, the 4F2 reactivity is confined to the basal layer. Cell suspensions of psoriatic epidermis demonstrated a greater percentage of reactivity with 4F2 (49.51% +/- 6.50%), probably reflecting the expanded population of basal layer cells. Monoclonal 4F2, therefore, reacts with a membrane antigen present on basal keratinocytes, and provides a probe for use in the isolation of the basal keratinocyte subpopulation. Thus, this antibody should be useful in studies of normal and aberrant differentiation of the epidermis.

Antibodies, Monoclonal↗
PubMed1984

Human medullary thyroid carcinoma in culture provides a model relating growth dynamics, endocrine cell differentiation, and tumor progression.

We used an unique model, human medullary thyroid carcinoma (MTC) in culture (the TT line), to study features of neuroendocrine-related biochemistry in relationship to growth, differentiation, and tumor progression. Tumor tissues from patients with virulent MTC contain a very heterogeneous distribution of cells staining for calcitonin (CT) and have a high ratio of intracellular L-dopa decarboxylase activity (DDC) to CT. We found, in a culture line of MTC derived from a patient with virulent disease, that the degree of the inverse relationship between DDC and CT and the heterogeneous cellular distribution of CT probably relate to the rate of cellular growth and the biochemical set of individual cell clones. During exponential growth of the parent TT cell line, intracellular DDC and CT varied. DDC increased by 70% and CT decreased by 40%. Single time-point measurements in 54 cell clones or highly enriched cell populations revealed a more dramatic variability for CT (15-fold) than for DDC (5-fold). During growth of the clones having the highest and lowest CT measurements, respectively, inverse dynamics between DDC and CT were again found. However, each clone maintained a distinct range of CT during the entire growth curve, with a 2- to 4-fold difference in CT between the two clones throughout. In the low producing CT clone, ratios between DDC and CT rose to greater than 1.0 during growth, a very high value found before this study only in MTC tissues from patients with virulent disease. Immunohistochemical staining for CT of parent cells and clones grown on embryonic chick skin revealed increased cellular heterogeneity for CT distribution during growth. The TT line provides a powerful tool to study neuroendocrine related biochemical events in relationship to growth, differentiation, and tumor progression in MTC. Our in vitro findings in the TT line well explain observations made previously in patients. We conclude that: (1) DDC, a neural property of MTC, is an early differentiation marker as compared to CT and that the differentiation status of MTC cells varies inversely with cell growth rate; and (2) in patients with MTC, the virulence of the tumor probably varies inversely with differentiation status. The inverse ratio of DDC to CT is probably determined in MTC by the proportion of rapidly growing cells and numbers of cell clones which have a poor ability for maturation.

Calcitonin↗
PubMed1984

Characterization of immature T cell subpopulations in neonatal blood.

A series of monoclonal antibodies directed against T cell differentiation antigens was used to identify circulating T cells in normal human neonates. Twenty-five cord blood samples, taken after cesarean or vaginal delivery, and 16 venous blood samples from normal adult controls were examined using monoclonal antibodies in an indirect immunofluorescence technique. The percentage of circulating OKT3 positive (pan-T cell) cells was significantly lower in the neonatal blood (52.8%) compared with the adult controls (74.9%) (P less than .001). Of the cord mononuclear cells, 58% showed reactivity with OKT10 (common thymocyte antigen) compared with only 7% in adult controls (P less than .001). The helper:suppressor T cell ratio was lower in cord blood (1:2) as compared with 1:3 for adult blood (P less than .005) as observed in these studies. These figures reflect the presence of a significant population (25%) of immature T cells in cord blood that expresses simultaneously both helper (OKT4) and suppressor (OKT8) phenotypes. Twenty-four percent of the T cells in cord blood also expressed OKT6 antigen (cortical thymocyte), a feature not found in adult blood. Double-labeling studies characterized a previously undescribed blood T cell phenotype, which was simultaneously OKT6 and OKT3 (pan-T cell) positive; of the cells reactive with OKT3, 43% also were positive with OKT6. This study reveals the presence of immature populations of T cells in normal human neonatal blood exhibiting phenotypes characteristic of normal developing thymocytes and a previously undescribed cell phenotype.

Adult↗
PubMed1984

Effect of monochromatic UVA light and 8-methoxypsoralen on human lymphocyte response to mitogen.

The ultraviolet-A (UVA) action spectrum for inhibition of DNA synthesis by lymphocytes stimulated with phytohemagglutinin and sensitized with 8-methoxypsoralen (8-MOP) (100 ng/ml) was determined by exposing cells to 0.33 and 1.0 J/cm2 of sub-bands of UVA light at 322, 334, 346, 358 and 370 nm. For lymphocytes irradiated with 0.33 J/cm2, the wavelength for optimal inhibition of DNA synthesis was 334 nm (P less than 0.001). Relatively high doses of monochromatic UVA light (6J/cm2) significantly inhibited lymphocyte proliferation at all wavelengths tested: 64% at 370 nm, 90% at 358 nm, 78% at 346 nm and greater than 99% at both 334 and 322 nm (P less than 0.001 at each wavelength). The optimal wavelength for selective 8-MOP enhanced inhibition of DNA synthesis by lymphocytes in the 334-346 nm range is shown to support the usual assumption that crosslinks represent a lethal cellular event.

DNA↗
PubMed1983

The diagnostic use of monoclonal antibodies in a variety of dermatologic conditions.

Monoclonal antibodies have been used to characterize subpopulations of lymphocytes in a variety of dermatologic conditions by immunofluorescence and immunoperoxidase staining. Various clinical presentations of cutaneous T-cell lymphoma have been shown to be neoplastic expansions of helper T-lymphocytes. Immunoperoxidase studies using subset-specific monoclonal antibodies have allowed the differentiation of patients with cutaneous T-cell lymphoma from lymphocytoma cutis and B-cell lymphomas secondarily involving the epidermis. Increased numbers of OKT-6 positive Langerhans' cells in the dermal infiltrates of patients with cutaneous T-cell lymphoma may be another immunocytological marker of this disease. Studies done on circulating lymphocytes of patients with psoriasis and pemphigus vulgaris have shown normal ratios of T-cell subsets in patients with psoriasis and an expansion of the helper T-cell subset in an untreated patient with pemphigus. Immunofluorescence and immunoperoxidase techniques used in conjunction with highly specific monoclonal antibodies have been shown to be valuable for histopathologic study of dermatologic diseases.

Antibodies, Monoclonal↗
PubMed1983

Thymopoietin-like substance in human skin.

A heterologous antithymopoietin (anti-TP) antibody was used to determine whether a TP-like molecule is present in the epidermis, since such factors have been postulated to play a part in known T cell-epidermal cell interaction. Examination of cytocentrifuge smears of freshly separated human epidermal cells stained by indirect immunofluorescence revealed that 8-14% of these cells possessed cytoplasmic reactivity with the anti-TP antibody. Similarly, 2-5% of human epidermal cells, maintained in tissue culture for 2-8 weeks, showed cytoplasmic staining with the anti-TP antibody. Double-labeling immunofluorescence studies, with the anti-TP antibody and a monoclonal antibody specifically reactive with Langerhans cells (OKT6), demonstrated that cells possessing this TP-like substance were not Langerhans cells. In situ studies of 4-microns frozen sections of normal human skin indicated that the cell population which possesses the TP-like substance is the basal layer of keratincoytes in the epidermis.

Fluorescent Antibody Technique↗
PubMed1983

Antigenic modulation of pan-T-cell and T-cell subset-specific markers.

The time course and extent of antigenic modulation induced by monoclonal antibodies OKT3, OKT4, OKT8, BE2, and BE3 was investigated. OKT3-induced antigenic modulation could be detected as early as after 3-hr incubation with the antibody and almost total removal of the OKT3-reactive antigen was seen by 42 hr. This modulation did not decrease the expression of T-cell antigens detected by OKT4 and OKT8. OKT3-modulated cells reexpressed the antigen after 42-hr incubation in OKT3-free media. BE3 (homologue of OKT1) also caused modulation of its surface antigen after 24-hr incubation. In contrast, OKT4 did not induce modulation even after 42-hr incubation with high concentrations of OKT4 antibody. Approximately 43% of the OKT8-reactive lymphocytes could be induced to modulate this antigen. A tumor-associated antigen present on neoplastic lymphocytes from patients with cutaneous T-cell lymphoma, recognized by monoclonal antibody BE2, also was not induced to modulate. These results suggest that antigenic modulation and the fate of the modulated antibody may be of importance to immunotherapeutic applications of these reagents.

Animals↗
PubMed1983

Recognition of immature T-cell phenotypes in neonatal blood using monoclonal antibodies.

The monoclonal antibody reactivity of cord blood mononuclear cells to six monoclonal reagents, OKT3, OKT4, OKT6, OKT8, OKT10, and OKT11, was evaluated using an indirect immunofluorescence technique. An immature population of cells was found; 24% of T cells in cord blood expressed OKT6 and 58% expressed OKT10. A previously undescribed phenotype, OKT3+/OKT6+, was discovered using double-labeling studies. In addition, the OKT4+:OKT8+ ratio in cord blood was 1:2, compared with 1:3 in the normal adult controls tested in this study. This is explained by the presence of a population of OKT4+/OKT8+ cells circulating in the neonate. Double-labeling studies of the cord blood samples demonstrated that all of the OKT3+ cells were simultaneously OKT11+ and that 17% of the cells were OKT11+ only. This is in accordance with the findings in normal adult peripheral T cells. Therefore, circulating neonatal T cells express an immature phenotype more characteristic of thymocytes and an altered OKT4+:OKT8+ ratio as compared with adult controls. We also describe a new phenotype OKT3+/OKT6+ present on the cord mononuclear cells.

Adult↗