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Biomedical subjects

C Riccardi

Publications and source records attributed to C Riccardi.

At least 127 records · Page 7Linked to original sources

Electrical behaviour of the rat's tibia during growth and fracture healing.

The electrical behaviour of the exposed tibial surface of young rats has been studied in normal conditions, after fracture and during the repair process. Recordings of potentials were made after all the electrical artefacts (muscle injury potentials) had been neutralized. No significant potential difference was obtained on the exposed bony surface in all the specimens. The results suggest that the currents of the hypothetical "bone-generator" do not reach the tibial surface. The bioelectrical properties of bone cannot therefore be investigated by an external recording method.

Animals↗

Metal ions in body fluids after arthroplasty.

We measured levels of metal ions in urine and plasma of 17 patients 7-15 years after they had a Co-Cr-Mo alloy total hip replacement. They had higher levels of cobalt and chromium than controls. No case of skin sensitivity to the investigated metals was observed. The values of cobalt and chromium in plasma and urine were considerably lower than in professionally exposed groups and do not represent a toxic hazard for the patients.

Aged↗

Studies on the mechanism of low natural killer cell activity in infant and aged mice.

NK activity in mice is high between about 6 and 10 weeks of age. In contrast, infant mice and mice older than 12-14 weeks of age usually have quite low or undetectable NK activity. Studies were performed to analyze the mechanisms underlying this characteristic age-related regulation of NK activity. Spleen cells from infant mice did not develop appreciable NK activity upon incubation for 12-18 h with either interferon (IFN) or interleukin-2 (IL-2). Analysis of the frequency of IL-2-dependent progenitors of NK cells, in a limiting dilution assay, also indicated that the spleens of infant mice are deficient in precursors of NK cells. In contrast, spleen cells from old mice (30 weeks old) developed substantial levels of NK activity upon incubation with either IFN or IL-2, and they showed a frequency of IL-2-dependent progenitors of effector cells that was similar to that of young mice. Both infant and old mice had plastic-adherent suppressor cells in their spleens, which could strongly inhibit NK activity. In addition, both infant and old mouse spleen cells contained nonadherent suppressor cells, which had a higher density on Percoll gradients than NK cells. Thus, several factors appear to contribute to the age-related regulation of NK activity in mice.

Age Factors↗

Reduced number of natural killer cells in patients with pathological hyperprolactinemia.

Human natural killer (NK) cell activity, as measured against K-562 target cells, was evaluated in 23 untreated and in 11 bromocriptine-treated hyperprolactinemic female patients and in 63 age-matched healthy women using 51Cr-release assay. The NK cell activity was significantly reduced in untreated hyperprolactinemic patients with respect to that of normal subjects, but therapy with bromocriptine restored NK cell function of patients to the levels of normal controls. Moreover, a reduced number of Leu-7+ cells and of large granular lymphocytes in hyperprolactinemic patients, as compared to normal controls and bromocriptine-treated subjects, correlated well with the decreased NK activity. Finally, 'in vitro' incubation with purified human prolactin, did not affect NK cell activity of blood mononuclear cells. The present results demonstrate that pathological hyperprolactinemia, in which a tuberoinfundibular dopaminergic defect has been postulated, is also associated with a reduction in NK cell number and function and indicate a possible interaction between prolactin, neuroendocrine system and NK cell lineage in man.

Antigens, Differentiation, T-Lymphocyte↗

Modulation of natural killer activity by thymosin alpha 1 and interferon.

A single injection of alpha beta-interferon (alpha beta-IFN) (30000 units/mouse), a major biological modifier of natural killer (NK) cytolytic activity, strongly stimulated NK activity in normal mice, as expected, while the same treatment did not statistically alter the NK response in cyclophosphamide (CY)-suppressed animals. We investigated the possibility of thymosin alpha 1 cooperating with alpha beta-IFN in boosting NK activity in CY-suppressed animals. The results show that treatment with thymosin alpha 1 (200 micrograms/kg) for 4 days, followed by a single injection of alpha beta-IFN 24 h before testing, strongly restored NK activity in CY-suppressed mice. Thymosin alpha 1 was, moreover, able to accelerate the recovery rate of NK activity in bone marrow reconstituted murine chimeras. Taken together the data support the concept that the synergic effect between thymosin alpha 1 and alpha beta-IFN could be the result of effects on differentiation of the NK lineage at different levels.

Animals↗

Modulation of polymorphonucleate-mediated cytotoxicity against Candida albicans by thymosin alpha 1.

In the present work we analyze the effects of thymosin alpha 1 treatment on the number and the candidacidal activity of murine polymorphonuclear leukocytes. The data we obtained showed that the treatment with thymosin alpha 1 (100 micrograms/Kg s.c.) 10, 8, 6, 4 and 2 days before the assay may result in a significant numerical augmentation of circulating polymorphonucleates in the peripheral blood, as well as of their candidacidal activity when measured in vitro in both a 4-h cytotoxicity assay and a CFU inhibition assay against Candida albicans microorganisms. On the other hand, a single dose of thymosin alpha 1 (500 micrograms/Kg s.c.) 3 days before the assay resulted in a significant decrease of the candidacidal activity of mouse polymorphonucleates. The data are discussed with regard to the immunomodulating capacity of thymosin alpha 1 and to our previously reported observations concerning the ability of the drug to modulate the resistance against systemic Candida albicans infection.

Animals↗

Increase of natural killer (NK) activity of mouse lymphocytes following in vitro treatment with cytosine-arabinoside.

The in vitro influence of cytosine-arabinoside (Ara-C) on mouse NK activity was studied treating effector cells, target cells or effector and target mixture with graded concentrations of the drug. Ara-C increased the NK efficiency of mouse splenocytes without enhancing the susceptibility of target cells or the cytolytic events when added to effector-target mixture. This phenomenon was confirmed with splenocytes collected from congenitally athymic (nude) or conventional donors of different ages, untreated or depressed or boosted for NK activity by various agents. In addition Ara-C increased the NK activity of spleen cells of nude mice deprived of nylon-adherent cells, and did not affect suppressor cells capable of inhibiting the lytic phase of NK process. The drug was able to significantly augment the binding ability of spleen cells to the NK-sensitive YAC-1 target. It was concluded that Ara-C would increase the efficiency of natural cytotoxicity presumably through a direct influence on effector lymphocytes.

Animals↗

Role of the thymus in the control of growth and differentiation of TCGF-sensitive natural killer (NK) cells.

We analysed the phenotypic characteristics of mouse NK cells susceptible to boosting activity by T-cell-growth-factor (TCGF) and the characteristics of NK-cell progenitors able to grow in vitro in the presence of TCGF. Our data show that while both the above-mentioned cell populations are Asialo GM-1+, they differ in the expression of Thy 1 alloantigen. In addition, we also analysed the possible regulatory mechanisms capable of influencing the growth of TCGF-sensitive NK-cell progenitors. The data here reported suggest that the growth capability of NK cell progenitors is under the control of the thymus.

Animals↗

Effects of interleukin-1 (IL-1) and interleukin-2 (IL-2) on the in vivo growth and differentiation of progenitors of natural killer (NK) cells.

We evaluated the possible modulating activity of interleukin-1 (IL-1) and interleukin-2 (IL-2) on in vivo growth of mouse progenitors of Natural Killer (NK) cells. Our data show that both IL-1 and IL-2 are able to stimulate the maturation of NK reactivity of infant mice as well as the regeneration of NK reactivity of lethally irradiated and reconstituted bone marrow chimeras.

Animals↗

Cloned lines of SJL/J spleen cells with cytotoxic reactivity.

Cultures of spleen cells from normal SJL/J mice were initiated and maintained in the presence of lectin-free interleukin-2 (IL-2). After about 8 weeks in culture, the frequency of progenitors of proliferative cells became quite high (1/8-1/10) and it was possible to obtain many clones by the limiting dilution technique. Some of the clones had high levels of cytotoxic reactivity against tumor target cells, even at low effector:target ratios, indicating that natural effector cells from this low-NK-reactive strain have the capability of expressing potent lytic effects. There was considerable heterogeneity among the clones in their patterns of cytotoxic activity, morphology and expression of T-cell-associated antigens. Although the overall pattern of reactivity resembled that of NK cells, some clones reacted against an anchorage-dependent lung cancer cell line, M109, without detectable effects against the other target cells tested, including the highly NK-susceptible lymphoma cell line, YAC-1. The pattern of cytotoxic reactivity by the clones did not correlate with the morphological appearance of large granular lymphocytes (LGL), which has been highly associated with NK activity of fresh, uncultured lymphoid cells.

Animals↗

Modulation of natural killer (nk) cell activity during FLV-P virus infection of mice.

We analyzed the effects of a polycythemic substrain of Friend leukemia virus, i.e. the FLV-P virus, on splenic NK activity of DBA/2 susceptible mice. One day after virus injection a significant increase of NK activity was found, which persisted until day 10. On the other hand, 14-21 days after virus injection a marked and significant depression of activity was measured. This depression was associated with the appearance of suppressor cells able to inhibit the lytic activity of untreated splenocytes when mixed in vitro in the 4 h 51Cr-release assay. The suppressor cell population was insensitive to treatment with anti-Thy 1.2 plus complement, was adherent to Sephadex G-10 and nylon, but did not adhere to plastic, suggesting it is neither a T-cell nor a typical macrophage. The possible relevance of NK activity modulation in relation to the induction of leukemia is discussed.

Animals↗

Metal determination in organic fluids of patients with stainless steel hip arthroplasty.

In 20 stainless steel Charnley hip arthroplasties (with a follow-up of 10-13 years) nickel, chromium and manganese levels were measured in blood, plasma and urine by atomic absorption spectrophotometry. Skin patch tests for these metals, and clinical and roentgenographic results of arthroplasty were also assessed. Metal levels in organic fluids were plotted against a control population homogeneous for age, residence and anamnestic conditions with the first, but which had never undergone a prosthesis or other metallic implant surgical procedure. Nickel levels in blood, plasma and urine, manganese levels in blood and urine and chromium levels in plasma were significantly higher in the hip prostheses population. Metal ion release from stainless steel prostheses is discussed with regard to implant failure, metal sensitivity and carcinogenesis.

Aged↗

Modulation of IL 2-dependent growth of mouse NK cells by interferon and T lymphocytes.

The regulatory role of interferon (IFN) on the growth of mouse natural killer (NK) cells in the presence of interleukin 2 (IL 2) was analyzed by the limiting dilution assay. Pretreatment for 5 hr with IFN (600 U/ml) was able to augment the frequency of proliferating cells and NK effector cells when spleen cells of BALB/c nu/+ and BALB/c nu/nu were cultured for 7 days in the presence of IL 2. When IFN was present during the 7-day culture period, we again found an increase in proliferative and cytotoxic frequencies in cultures of spleen cells from nude mice, but in contrast, found a decrease in these frequencies in cultures of spleen cells from euthymic mice. Addition of irradiated (3000 R) spleen or thymus feeder cells from euthymic mice to the nu/nu cultures caused an inhibitory activity of IFN also on nu/nu cells. These data indicate that IFN can have both positive and negative regulatory effects on the in vitro growth and differentiation of mouse NK cells and that the inhibitory effects are mediated via T lymphocytes.

Animals↗

Limiting dilution analysis of the frequency of human T cells and large granular lymphocytes proliferating in response to interleukin 2. II. Regulatory role of interferon on proliferative and cytotoxic precursors.

Limiting dilution analysis has shown that large granular lymphocytes (LGL) and small T cells undergo proliferation in response to lectin-free IL 2. The latter is critically dependent on prior stimulation with lectin. Depending on conditions, alpha or beta interferons (IFN) were found to have either of two opposing effects on the frequency of proliferating cells. Pretreatment of responder cells with IFN resulted in dose-dependent augmentation of proliferative progenitors such that at 500 IU/ml, a fivefold increase of progenitor frequency was apparent. Under such conditions, approximately 5% of LGL could be expanded, and at least a proportion of the cultured cells killed the NK-sensitive K562 cell line. Similar results were apparent with T cell responders: whatever the initial frequency of proliferation (dependent on the PHA dose), augmentation was obtained with IFN pretreatment, although no killing of K562 was induced. In contrast, when IFN was present throughout the 7-day assay period, proliferative frequencies were reduced. This inhibitory effect was mediated through the presence of irradiated T cells in the feeder populations. With purified monocytes as feeder cells, little reduction was seen, whereas addition of T cells resulted in a 19-fold inhibition. Separation of OKT4+ and OKT8+ subsets demonstrated that both were essential for optimum induction of suppression. These data indicate that IFN has a powerful immunodulatory role on both NK and T cell proliferation, and that it may function both by induction of IL 2 receptors and activation of suppressive T cells. The interaction between different soluble mediators provides a complex immunoregulatory circuit in vitro.

Hematopoietic Stem Cells↗

Comparison between natural reactivity (NR) against Candida albicans and natural killer (NK) activity against YAC-1 tumour cells.

Cytotoxic activity against Candida albicans was measured in vitro in a 4-h 51Cr-release assay. The levels of reactivity correlated well with the number of polymorphonuclear cells in the effector population, being augmented by the enrichment of polymorphonuclear granulocytes. To exclude the possible role of contaminating natural killer cells, natural killer activity against tumour cells was compared with natural reactivity against Candida albicans in vitro. The findings indicate that there are many differences between these reactivities including organ and strain distribution, age dependency, adherence to nylon, and susceptibility to modulation by immuno-adjuvants and to treatment with anti-Thy 1.2 antiserum plus complement. These data further define in vitro polymorphonucleate-mediated cytotoxicity against Candida albicans on the basis of the above-mentioned criteria and clearly demonstrate that this in vitro reactivity could not be due to the presence of contaminating natural killer cells in the effector cell population.

Age Factors↗

Suppression of natural killer (NK) activity by splenic adherent cells of low NK-reactive mice.

Adherent cells with the ability to inhibit NK activity were found in the spleens of young 8-week-old SJL/J mice. Such suppressor cells were also found in the spleens of other low-NK-reactive strains, but not in the spleen of age-matched high-NK-reactive strains. These suppressor cells had the characteristics of macrophages, since they were plastic- and nylon-adherent, phagocytosed latex and iron particles, and were resistant to treatment with anti-Thy-1.2 serum plus complement. Their inhibitory activity appeared to be due to their production and/or release of soluble suppressive factor(s). Their suppressor activity was similar to that of pyran copolymer-activated macrophages, which were previously shown to be suppressive for cytotoxicity by NK cells. We suggest here that macrophages may be involved in the physiological regulation of NK activity and may contribute to the low NK activity in some strains of mice.

Animals↗