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C Jemma

Publications and source records attributed to C Jemma.

36 records · Page 2Linked to original sources

In vitro and in vivo immunomodulatory activity of an N-9 arginyl hypoxanthine derivative (PCF-39).

A new synthetic derivative, N-alpha-5 (1,6-dihydro-6-oxo-9-purinyl) pentyloxy-carbonyl-L-arginine (PCF-39) has been evaluated in vitro and in vivo in order to clarify its immunopharmacologic profile. In vitro, PCF-39 did not modify spleen cell functions, whereas parenteral administration in mice of 2.5 and 25 mg/kg (50 and 500 micrograms/mouse) induced an increase in spleen and lymph node cellularity that resulted in a significant resistance to the growth of two distinct syngeneic transplanted tumors. These in vivo findings show that PCF-39 is a potent immunotherapeutic agent with an antitumor effect.

Adenocarcinoma↗

Serial transplantation of a human acute T lymphoblastic leukemia into nude mice.

A human acute T lymphoblastic leukemia line (PF-382) was serially transplanted into nude mice. No takes were observed in untreated nude mice, whereas solid tumors were observed in splenectomized and total body, sublethally irradiated mice. The minimal tumor-inducing dose and the latency time remained unchanged after the third and fifth serial transplants. Moreover, leukemic cells recovered from the 8th in vivo passages displayed the same differentiation antigens and chromosomal markers as the in vitro PF-382 cell line used for the first transplant. This stable and well-characterized experimental system could be a new model for T-lymphocyte differentiation and immune-reactivity against human leukemias.

Animals↗

Fluctuations of NK activity in human volunteers receiving vitamin A or a placebo daily.

This paper examines the effect of prolonged daily administration of Vitamin A on NK activity. A placebo and a pill containing 50,000 IU retinol acetate (RA) were taken daily for 120 days by 5 and 6 healthy volunteers respectively. NK activity was determined on days -45, -40, -30 and -10 to calculate each volunteer's inherent variability and then twice a month throughout the administration period. To minimize the experimental variability, an internal control was inserted in each assay. This consisted of two lymphocyte preparations from two healthy individuals divided into cryopreserved aliquots. The cytotoxicity percentage in each assay was corrected against these reference standards and converted into NK values by angular transformation. No increase in NK activity was noted during the study in the group receiving RA. A marked individual variability, however, was noted in both groups.

Female↗

Establishment of the antiviral state in alpha, beta-interferon-resistant Friend cells treated with gamma-interferon. Induction of 67-kilodalton protein kinase activity in absence of detectable 2-5A synthetase.

Treatment with murine gamma-interferon (IFN) preparations of variant sublines of Friend leukemia cells resistant to the alpha, beta IFN-induced antiviral state (Affabris, E., Jemma, C., and Rossi, G.B. (1982) Virology 120, 441-452; Affabris, E., Romeo, G., Belardelli, F., Jemma, C., Mechti, N., Gresser, I., and Rossi, G. B. (1983) Virology 125, 508-512) results in the establishment of a bona fide antiviral state. In fact, gamma IFN preparations are able to induce a dose-dependent reduction of endogenous virus release and of vesicular stomatitis or encephalomyocarditis viruses yields (up to 1.5 log). Under these experimental conditions, no inducible 2-5A synthetase activity is detectable in cell extracts. The 67-kDa protein kinase, uninducible by treatment with alpha, beta IFN (up to 13,000 units/ml), is instead induced upon treatment with gamma IFN at a similar rate of activity as in wild-type Friend leukemia cells, both when assayed in solution and after immobilization on poly(rI) X poly(rC)-agarose.

2',5'-Oligoadenylate Synthetase↗

Functional properties in Sézary cells with an unusual phenotype.

The immunological and functional characteristics of Sézary cells with an unusual phenotype are reported. The clinical, histologic, and hematologic picture was typical for Sézary syndrome. Studies with monoclonal antibodies showed that 80% Sézary cells had an CD3+, CD4+, CD5+, CD7-, CD8-, Leu-7+, Leu-8-, Leu-11-, OKM1- phenotype. By two-color immunofluorescence assay 80% FACS-sorted Leu-7+ cells coexpressed CD4 antigen and did not express the myeloid antigen OKM1, CD8, and antigens characteristic of immature T cells. The cells had no NK activity but did display a high helper activity. Unseparated and FACS-sorted Leu-7+ and Leu-7- Sézary cells did not respond to mitogens but were able to grow in the presence of exogenous IL-2. FACS sorted Leu-7- cells, cultured for 7 days in the presence of 20% IL-2, acquired the receptors for Leu-7. IL-2 and IFN-gamma production was studied in unseparated Leu-7+ and Leu-7- FACS-sorted Sézary cells. IL-2 production was lower than in normal cells. The addition of PHA or PHA plus TPA led to an increase in IL-2 production. Also IFN-gamma production was marked lower than in normal controls but increased after 7-day culture in exogenous IL-2. In conclusion in this case the Sézary cells may represent a neoplastic expansion of the CD3+, CD4+, CD5+, Leu-7+, Leu-11- subpopulation which is equivalent to the 2-4% of the Leu-7+ population in normal lymphocytes.

Aged↗

Interleukin 2 (IL 2) and interferon-gamma production by T lymphocytes from patients with B-chronic lymphocytic leukemia: evidence that normally released IL 2 is absorbed by the neoplastic B cell population.

The capacity of T lymphocytes from patients with B cell chronic lymphocytic leukemia (B-CLL) to release interleukin 2 (IL 2) and interferon (IFN)-gamma was assessed following various stimuli. The spontaneous release of IL 2 and IFN-gamma was practically absent both with B-CLL and normal T lymphocytes. By contrast, after stimulation with phytohemagglutinin (PHA) or with PHA plus 12-O-tetradecanoylphorbol-13-acetate, the production of IL 2 and IFN-gamma by B-CLL T lymphocytes was similar to that of normal T lymphocytes, irrespective of the reversed T lymphocyte subset distribution (OKT4/OKT8 ratio) observed in B-CLL. However, the titer of IL 2 was greatly reduced when autologous leukemic B cells were added to the culture system. Unlike IL 2, the presence of leukemic B cells did not affect the titer of IFN-gamma in the culture supernatants. The indication that IL 2 may be adsorbed in vivo by the neoplastic B cells was further confirmed by the demonstration of the IL 2 receptor (revealed by anti-Tac monoclonal antibody) on the leukemic B cells, particularly following mitogenic stimulation, and by the evidence that exogenous IL 2 can be directly absorbed by untreated B-CLL T lymphocytes to release IFN-gamma and IL 2 is preserved, but that IL 2 may be rapidly removed by the neoplastic B-CLL cells, thus contributing to the well-documented T lymphocyte abnormalities present in this disease.

Absorption↗

2-5A synthetase activity does not increase in interferon-resistant Friend leukemia cell variants treated with alpha/beta interferon despite the presence of high-affinity interferon receptor sites.

The presence of interferon (IFN) receptors on mouse Friend leukemia cells (FLC) has been investigated in binding experiments with highly purified 125I-labeled mouse alpha/beta IFN. Both IFN-resistant clones and wild-type IFN-sensitive FLC showed a specific saturable binding site for mouse IFN with a similar affinity constant. In contrast to IFN-sensitive FLC, IFN-resistant FLC variants were not inducible by IFN for double-stranded RNA-dependent 2-5A synthetase activity.

2',5'-Oligoadenylate Synthetase↗

Growth and differentiation of Friend erythroleukemia cells in serum-free culture.

A synthetic medium allowing indefinite optimal growth of Friend erythroleukemia cells (FLC) is described. It consists of Iscove's modified Dulbecco's medium supplemented with bovine serum albumin, transferrin, and a lipid mixture. Transferrin and lipids are essential for Friend cells growth. Under these conditions, FLC erythroid differentiation, promoted by a number of inducers, is less efficient than in cultures with serum-rich medium, suggesting that unknown serum factors may play an additional role in this phenomenon. Conversely, the enhancement of erythroid differentiation induced by low doses of Interferon is superimposable in both types of cultures.

Animals↗

Interleukin-2 injected around tumor-draining lymph nodes in head and neck cancer.

Twenty patients with recurrent, inoperable head and neck squamous cell carcinoma received perilymphatic injections of natural interleukin-2 (nIL-2) for 10 days. Ten patients received 200 units (U) of nIL-2; five 1,000 U; and five 5,000 U. Irrespective of the location of the recurrence, the injections were always performed 1.5 cm below the insertion of the sternocleidomastoid muscle on the mastoid. When the ipsilateral lymphatic chain was still present, they were performed on the same side as the tumor site, whereas when it had been stripped as a result of previous surgery, they were contralateral. Patients who had undergone bilateral neck dissection were injected on the tumor side. Whenever possible, the treatment was repeated after 45-day intervals. In 13 patients (65%) with bilateral or contralateral lymph nodes, complete or partial disappearance of the lesion was observed. Despite these marked responses, the tumor always relapsed, and subsequent IL-2 courses were poorly effective. There were no systemic disturbances during or after treatment, but only moderate local swelling and pain.

Adult↗

Xenotransplantation in immunosuppressed nude mice of human solid tumors and acute leukemias directly from patients or in vitro cell lines.

Athymic nude (nu/nu) mice are widely employed for the heterotransplantation of human tumor cell lines established in vitro and tumor cells directly grafted from patients. By contrast, hemopoietic malignancies have consistently proved difficult to transplant and well-characterized human leukemias suitable for studies in nude mice are scarce. We report here our experience with subcutaneous xenotransplantation of human neoplastic cells into nu/nu mice immunosuppressed through sublethal irradiation and splenectomy (SI-nu/nu) and with an additional injection of anti-Asialo-GM1 antibodies (SIA-nu/nu) in order to eliminate natural killer activity. Thirteen out of 16 continuous cell lines established in vitro from solid tumors and 7 out of 14 human tumors obtained from fragments of surgical specimens formed a progressively growing tumor in SI-nu/nu mice. Six out of 8 in vitro established human leukemic cell lines and 5 out of 18 neoplastic hematopoietic cells directly xenotransplanted from the patient grew SIA-nu/nu mice. When the membrane and chromosome markers of neoplastic cells that grew into the mice were evaluated, only marginal differences with those of the original tumors were found. In addition, when interfering factors alter the histological aspect of the primary tumor, xenotransplantation may also be of some help in histological diagnosis. By using SI- and SIA-nu/nu mice, it is thus possible to build up several new in vivo experimental systems with fresh human tumors that may be of value in studying the efficacy of differentiation factors and immunological maneuvers on the in vivo growth of human tumors.

Animals↗

Replication of HHV-6 in cord blood lymphocytes and Jurkat cells.

Replication of HHV-6 in cord blood lymphocytes (CBL) and Jurkat cells has been studied by comparing their infection rate and susceptibility. Jurkat cells were less susceptible to HHV-6 infection and CBL cell cultures stimulated with PHA proved more sensitive culture for its isolation.

Antibodies, Monoclonal↗

[Macrophage activation and lymphokine production in the mouse by lymphocytes sensitized against Trichomonas vaginalis].

In this study we have examined whether resident peritoneal macrophages could be activated in vitro by immune T lymphocytes obtained from mice which were immunized with live Trichomonas vaginalis (T. vaginalis). T lymphocytes obtained from mice previously sensitized against T. vaginalis, showed a significant proliferative response when cultured in vitro in the presence of T. vaginalis. Resident peritoneal macrophages obtained from untreated syngenic Balb/c mice revealed an increasing cytotoxic activity against the protozoa when seeded with increasing concentrations of purified immune T lymphocytes and a constant number of H3 thymidine-labeled T. vaginalis. This cytotoxicity was detectable after 24 h of culture and peaked after 48 h. Supernatants obtained from cocultures of macrophages, immune T lymphocytes and T. vaginalis contained gamma-Interferon and TNF alpha/beta.

Animals↗

[Perilymphatic injection of interleukin-2 (IL-2) in recurrent squamous cell carcinoma of the head and neck].

Twenty patients with recurrent squamous cell carcinoma of the head and neck received daily injections of interleukin-2 (IL-2) from the Jurkat T-cell line, purified by high pressure liquid chromatography for 10 days. Two hundred (ten patients), one thousand (five patients) and five thousand (five patients) units of IL-2 in 0.5 ml were injected 1.5 cm from the point where the sternocleidomastoid muscle inserts itself on the mastoid. Whenever possible, the treatment cycles were repeated at 45 day intervals. In 13 patients with contralateral or bilateral cervical lymph nodes, complete or partial disappearance of the tumor was observed. There were non systemic disturbances after injection and only moderate local swelling and pain.

Adult↗