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Biomedical subjects

G Melioli

Publications and source records attributed to G Melioli.

At least 91 records · Page 5Linked to original sources
PubMed1983

Generation of CFUC suppressor T cells in vitro: VII. T derived colony inhibitory activity (Td/CIA) has no suppressor effect on in vitro immunoglobulin production.

T derived colony inhibitory activity (Td/CIA) was obtained from unstimulated T cells from aplastic anemia patients (SAA), or from PWM primed normal T cells. Td/CIA suppressed CFUC growth of normal allogeneic marrow to less than 30% of expected growth. Td/CIA was then added to normal peripheral blood T and B cells, primed with PWM, to test whether it would interfere with in vitro immunoglobulin (Ig) production. When Td/CIA from normal T cells was added to cultures of T + B cells + PWM there was a 2-2.1-fold increase in Ig production. Similarly the addition of Td/CIA from SAA patients also resulted in a 1.4 up to 166-fold increase in Ig production. These results indicate that either (a) the targets for Td/CIA are expressed on hemopoietic but not on T and B cells, or (b) that Td/CIA inactivates an accessory cell which is essential for CFUC growth but not for the PWM driven in vitro B cell differentiation system.

Anemia, Aplastic↗
PubMed1982

Surface markers of cloned human T cells with helper or suppressor activity on pokeweed mitogen-driven B cell differentiation.

Human spleen T cells stimulated with pokeweed mitogen (PWM) were cloned under limiting conditions in microculture systems using interleukin 2 and irradiated autologous cells. Clones were screened for helper or suppressor activity on PWM-dependent B cell differentiation by adding cell aliquots to either isolated B cells and PWM or to mixtures of T and B cells and PWM. Out of 97 clones tested, 14 promoted intense B cell differentiation, as assessed by measurements of secreted IgG, and 6 strongly inhibited B cell maturation induced by spleen T cells. All the selected clones maintained their original activity after short-term clonal expansion; in addition, a similar (helper or suppressor) effect was detected when the total number of plasma cells per well was evaluated. Suppressor clones had no cytolytic activity on autologous T and B cell blasts, K562 cells or antibody-coated L 1210 mouse cells. Nine helper and 6 suppressor clones were analyzed for a battery of surface markers. All the clones were E rosette-positive and expressed HLA-DR (Ia) antigens. Fcmu receptor was present on a single helper clone, whereas Fc gamma receptor was expressed on a suppressor clone only. All but two clones expressed the OKT4+/ OKT8-, a single suppressor clone was OKT8+/OKT4-, whereas coexpression of OKT4 and OKT8 antigens was detected in one helper clone. Thus, the claim that helper T cells are OKT4+/OKT8- and suppressor T cells are OKT4-/OKT8+ is not supported by the analysis of their phenotype at the clonal level.

Antibodies, Monoclonal↗
PubMed1982

Abnormalities of immunocompetent cells in primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is a chronic cholestatic progressive liver disease frequently associated with various immunological abnormalities. We have studied the influence of normal and PBC adherent cells (AC) on peripheral blood lymphocytes (PBL) colony growth both in liquid and soft agar culture. Co-culture experiments with different combinations of AC and PBL of PBC patients and normal donors provided evidence that PBC adherent cells function abnormally. However, this impaired function is not the sole factor involved, since the number of colonies formed by PBC lymphocytes in the presence of normal AC was twice the normal value. The possibility that this increase is correlated with the state of activation of T cells is discussed in the light of the high number of DR-positive T cells found in the PBC patients studied. Finally, none of these immunological abnormalities was related to the stage of the disease.

Adult↗
PubMed1979

Imbalances of T cell subpopulations in patients with atopic diseases and effect of specific immunotherapy.

Reduced numbers of T cells with Fc receptors for IgG (TG cells) are present in blood samples of patients with respiratory allergic disease, mainly those with severe symptoms. TG cells have been previously shown to be suppressor in the pokeweed mitogen- (PWM) dependent B cell differentiation. T cells with Fc receptor for IgM (TM cells), which help immunoglobulin production, are in a normal range. After specific hyposensitization, resulting in a sharp improvement of clinical symptoms, TG cell subset reached normal values.

Adolescent↗
PubMedDate not supplied

Anti-human thyroglobulin autoantibodies assayed by an enzyme-linked immunosorbent assay.

A rapid and simple enzyme-linked immunosorbent assay (ELISA) for anti-thyroglobulin IgG antibodies is described. The method is based on a 'sandwich' using purified human thyroglobulin adsorbed to polystyrene microplates, human serum and anti-human IgG antiserum conjugated to alkaline phosphatase. The sensitivity of the method is about 8 ng/ml, as evaluated with a purified anti-thyroglobulin antibody preparation. High concentrations of antibodies were observed, as expected, in autoimmune thyroid disease; however, the majority of normal subjects have detectable, although very low, antibody levels. We conclude the method is suitable for current clinical use.

Antibodies, Anti-Idiotypic↗
PubMedDate not supplied

Intraperitoneal infusion of interleukin-2 in patients with malignant ascites: phenotypic and functional effects on tumor-associated lymphocytes.

The aim of the present study was to evaluate the effects of intraperitoneal interleukin-2 (IL-2) infusion on tumor-associated lymphocytes (TAL) and peripheral blood lymphocytes (PBL) in patients with malignant ascites. Six patients were given IL-2 daily for 14 days by intraperitoneal infusion using a delivery system. TAL were isolated from the ascitic fluid before (day 0) and 7 and 14 days after the initiation of the treatment. Although no variations were observed in cytolytic activity and surface markers of PBL, TAL showed an important increase in the percentage of cells expressing IL-2 receptors of lymphokine-activated killer (LAK)-1 antigen (i.e., a surface molecule expressed by human LAK cells and their precursors). Perhaps more importantly, a sharp increase of natural killer activity and the de novo generation of LAK activity were also observed.

Ascites↗
PubMedDate not supplied

Phenotypic and functional heterogeneity of human T cell clones producing gamma-interferon.

Human T cell clones were derived from peripheral blood and screened for their ability to release gamma-interferon (gamma-IF) following PHA stimulation. Nine clones producing more than 20 U/ml of gamma-IF were expanded and analyzed for cytolytic activity in a lectin-dependent assay and for the ability to release interleukin-2 (IL-2). In addition, clones were analyzed for T4 and T8 antigen expression. Five out of nine clones had cytolytic T lymphocyte activity, while four released relatively large amounts of IL-2. Five clones were T4+ while the remaining expressed the T8+ phenotype. These results clearly indicate that gamma-IF production is not restricted to T cell subsets defined according to either functional or phenotypic criteria.

Clone Cells↗
PubMedDate not supplied

Adoptive immunotherapy with tumor-infiltrating lymphocytes and subcutaneous recombinant interleukin-2 plus interferon alfa-2a for melanoma patients with nonresectable distant disease: a phase I/II pilot trial. Melanoma Istituto Scientifico Tumori Group.

BACKGROUND: On the basis of our previous experience, we designed this study to determine the activity and toxicity of outpatient treatment with autologous tumor-infiltrating lymphocytes (TIL) together with intermediate-dose recombinant interleukin-2 (rIL-2) and low-dose recombinant interferon alfa-2a (rIFN-alpha2a), for patients with metastatic melanoma. METHODS: Between April 1992 and October 1994, we processed 38 melanoma samples derived from 36 patients with metastases. Proliferative cultures of expanded lymphocytes (TIL) were infused only once into patients with metastatic melanoma. rIL-2 was administered subcutaneously for 1 month, starting on the day of TIL infusion, at an escalating dose of 6-18 x 10(6) IU/m2/day for the first week and at the maximum-tolerated dose for the subsequent 3 weeks and then, after a 15-day interval, for 1 week/month for 3 months. rIFN-alpha2a was administered subcutaneously at 3 X 10(6) IU three times each week until progression. RESULTS: Of 38 melanoma samples, 19 (50%) resulted in proliferative cultures and were infused. The median number of expanded lymphocytes was 18 x 10(9) (range, 1-43 x 10(9)), and the median period of culture was 52 days (range, 45-60). rIL-2 was administered at doses ranging between 6 and 18 x 10(6) IU/m2/day. Toxicity was mild or moderate, and no life-threatening side effects were encountered. Two of 19 treated patients experienced complete responses of their metastatic sites (soft tissue), 10 had stable disease, and 7 showed progressive disease. The response rate was 11% (95% confidence interval, 2-35%). CONCLUSIONS: Outpatient treatment with TIL plus rIL-2 and rIFN-alpha2a is feasible, although, within the context of the small sample size, the activity of the combination was no different from the reported activity of any of the components used alone.

Adult↗
PubMedDate not supplied

Adoptive immunotherapy of advanced solid tumors: an eight year clinical experience.

BACKGROUND: Adoptive immunotherapy (AI) of cancer, based upon the injection of in vitro manipulated autologous lymphocytes is still in an experimental phase. Our group started different clinical trials of AI in early 1990, and, at present, some specific targets for this approach seem to have been identified. PATIENTS AND METHODS: 296 patients with solid tumors (melanoma, kidney carcinoma, non-small-cell lung cancer, mesothelioma, neoplastic pleural effusion, and liver cancer) were treated with either locoregional or systemic adoptive immunotherapy (AI) using both LAK and TIL cells in combination with s.c. rIL-2. RESULTS: The surgery/AI combination resulted in good clinical results, characterized by enhanced survival and long lasting disease free periods in a significant number of patients. CONCLUSIONS: AI seems to be efficacious in the treatment of melanoma, lung and hepatic cancers. Further studies will expand the application of the treatment to other malignancies.

Clinical Trials as Topic↗
PubMedDate not supplied

Phenotypic and functional characterization of human T lymphocytes expressing a gamma/delta T cell antigen receptor.

Most mature T lymphocytes express CD3-associated antigen receptor molecules (TCR) formed by alpha and beta chains. Recently, a minor subset has been identified that express a different CD3-associated TCR composed of gamma and delta chains. The cell subset expressing TCR gamma/delta differs from conventional T cells in a number of phenotypic and functional characteristics. The simultaneous lack of both CD4 and CD8 antigens at the cell surface allows one to greatly enrich for TCR gamma/delta + cells (by monoclonal antibodies, mAbs and complement). Cloning of CD4-8- peripheral blood lymphocytes revealed that they are homogeneously composed of cytolytic cells which, in most instances, lyse tumor target cells. TCR gamma/delta + cells proliferated in response to allogeneic cells in mixed lymphocyte culture (MLC) and MLC-derived TCR gamma/delta + cells specifically lysed PHA-induced blast cells bearing the stimulating alloantigens, thus providing the formal proof that they recognize (allo)antigens. The use of different mAbs specific for TCR gamma/delta molecules allowed us to identify two distinct subsets which bound BB3 and delta-TCS-1 mAbs, respectively. The BB3-reactive molecules in peripheral blood-derived TCR gamma/delta + cells were represented by C gamma 1-encoded disulphide-linked heterodimers, whereas delta-TCS-1 reacted with C gamma 2-encoded non disulphide-linked molecules. Both BB3 and delta-TCS-1 mAb induced activation of cloned cells expressing the corresponding antigenic determinants (as assessed by measurements of intracellular Ca++ and/or lymphokine production or cytolytic activity).(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMedDate not supplied

Interferons in the treatment of advanced breast cancer.

In the past two decades interferons have undergone extensive phase I and II evaluations in various types of cancers, including breast cancer. This article reviews the experience, obtained from preclinical and clinical studies, about the clinical rationale efficacy and toxicity of interferons in cancer treatment. In particular, we examine the preclinical experience in which antineoplastic activity of interferon against breast cancer has been demonstrated. Finally we discuss clinical data accumulated using interferon-alpha, interferon-beta and lymphoblastoid interferon alone or in combination in metastatic breast cancer patients. The use of the interferons in the treatment of breast cancer remains investigational and the optimal scheduling undetermined. New methods of administration may maximize the antitumor effects in order to better understand the role of interferon in clinical oncology.

Breast Neoplasms↗
PubMedDate not supplied

Effect of granulocyte-macrophage colony-stimulating factor on growth of a xenotransplanted human ovarian cancer cell line IGROV-1 in nude mice.

The clonal growth of cell lines derived from human ovarian tumours can be stimulated by GM-CSF in vitro. Among these cell lines one of the most responsive is the IGROV-1 cell line. This report describes the influence of GM-CSF on the in vivo growth of IGROV-1 cell xenografts in nude mice. Beginning one day after transplantation of the tumour, the cytokine was administered daily for 31 consecutive days as i.m. injections distant from the tumour lesion at doses of 0.1 microgram/kg and 1 microgram/kg. GM-CSF caused no significant effects on the growth modulation of the ovarian cancer cells in vivo.

Animals↗