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Biomedical subjects

C Riccardi

Publications and source records attributed to C Riccardi.

At least 109 records · Page 6Linked to original sources

Immunosuppressive effect of cyclosporin A on resistance to systemic infection with Candida albicans.

We studied the influence of cyclosporin-A (Cy-A) on resistance of mice to systemic infection with Candida albicans. Cy-A clearly inhibited resistance to C. albicans. The effect was dose-dependent and time and route of administration of the drug were important. This immunodepressive effect was due, at least in part, to an impairment of polymorphonuclear leucocyte (PMNL) candidacidal activity, as demonstrated in vitro by a reduction of phagocytic and cytotoxic activity and in vivo by protection when PMNL from untreated mice were transferred into cyclophosphamide-treated hosts challenged with C. albicans. The decreased activity of PMNL could be partly restored by adoptive transfer of normal T-lymphocytes into Cy-A-treated mice, as well as by exposure of PMNL to gamma-interferon (IFN-gamma) in vitro.

Animals↗

Evolutionary conservation in various mammalian species of the human proliferation-associated epitope recognized by the Ki-67 monoclonal antibody.

The human proliferation-associated epitope recognized by the Ki-67 monoclonal antibody (MAb) was detected in proliferating normal and neoplastic cells of many mammalian species (lamb, calf, dog, rabbit, rat) besides human. In contrast, Ki-67 stained proliferating cells from other species weakly (mouse) or not at all (swine, cat, chicken, pigeon). The immunostaining pattern of Ki-67 in animal tissues was identical to that previously described in human: Ki-67 reacted only with cells known to proliferate (e.g., germinal center cells, cortical thymocytes) but not with resting cells (e.g., hepatocytes, brain cells, renal cells); this MAb produced a characteristic nuclear staining pattern (e.g., stronger labeling of nucleoli than of the rest of the nuclei and staining of chromosomes in mitotic figures); and Ki-67 crossreacted with the squamous epithelium in both animal and human tissues. In vitro studies showed that when quiescent (Ki-67-negative) NIH 3T3 fibroblasts or bovine peripheral blood lymphocytes were induced to proliferate, the appearance of Ki-67-positive cells paralleled the induction of cell proliferation caused by addition of fetal calf serum or PHA, respectively, to the cultures, and in both human and rat proliferating cells the Ki-67 expression closely paralleled the incorporation of [3H]-thymidine. These findings indicate that the epitope recognized by the Ki-67 MAb in human and animal species is the same. The widespread evolutionary conservation of the human proliferation-associated epitope recognized by the Ki-67 MAb suggests that it and/or its carrier molecule may play an important role in regulation of cell proliferation.

Animals↗

Effect of various cytokines and growth factors on the interleukin-2-dependent in vitro differentiation of natural killer cells from bone marrow.

We have studied the possible role of various cytokines and growth factors on the in vitro interleukin-2 (IL-2)-dependent development of natural killer (NK) cells from bone marrow precursors. Our results indicate that tumor necrosis factor alpha and lymphotoxin augment the generation of NK cells. In contrast, interleukin-4, transforming growth factor beta and granulocyte-macrophage colony-stimulating factor significantly inhibit this phenomenon. Other factors tested, such as epidermal growth factor and fibroblast growth factor, did not detectably influence the IL-2-dependent development of NK cells.

Animals↗

In vitro proliferation of human large granular lymphocytes with v-raf/v-myc recombinant retrovirus.

The effect of infection with a retrovirus carrying v-raf/v-myc oncogenes (J2 virus) on the in vitro proliferation of human large granular lymphocytes (LGL) was investigated. LGL infected with J2 virus (J2LGL), unlike uninfected cells, grew with a proliferation peak eight days after infection. Such cells retained the morphology and functional properties typical of LGL. Furthermore, 5% of J2LGL produced virus the day after infection, whereas non-virus production was detectable five days later. These data indicate that J2 virus provides a transient mitogenic signal for LGL.

Cell Division↗

Role of interferons in natural killer cell generation from primitive bone marrow precursors.

We studied the possible role of interferons (IFNs) on the interleukin-2 (IL-2)-dependent development of mouse natural killer (NK) cells from undifferentiated bone marrow (BM) precursors. Results indicate that alpha-IFN is able to synergize with IL-2 in the induction of lytic effectors. The stimulating effect of alpha-IFN is dose-dependent and is also obtained when BM cells are pretreated shortly before culturing. The precursor cells are resistant to treatment with 5-fluorouracil (FU, 150 mg/kg i.v.). Treatments which have been shown to eliminate more differentiated cells but spare less differentiated BM precursors, are asialoGM1-, Thy1+, Lyt1- and Lyt2-. Effector cells generated by culturing with IL-2 and alpha-IFN are typical NK cells in that they lyse only NK-susceptible targets. These are Thy1+, asialoGM1+, Lyt5+, Lyt1- and Lyt2-. These data suggest that alpha-IFN may represent a maturational signal for the generation of NK cells from undifferentiated BM precursors.

Animals↗

Evaluation of reimplant total hip prostheses and resection arthroplasty.

Results of reimplanted total hip prostheses and resection arthroplasty were compared. Using the Iowa hip rating scale, the reimplanted prostheses population was rated higher for function, gait, and absence of deformity, however, the resection arthroplasty population rated better in freedom from pain. Radiographic findings in the reimplanted prostheses population included radiolucent lines around the cement, loosening, and cortex bone stock loss. These findings cause concern for the future of these implants. Repair and remodeling of the bone lesions were observed in resection arthroplasties. It was concluded that if healing of infection is achieved or if resection is performed for mechanical failure, the results may be considered permanent.

Adult↗

Isoelastic shoulder prostheses. Considerations on use and results.

The principles underlying the use of isoelastic shoulder prostheses are discussed and the results obtained in 8 patients are reported. Two operations were for pseudarthrosis of the humeral neck and 6 for osteolytic neoplasms. The results were assessed after an average follow-up of 4 years. Full movement was never recovered; there was partial recovery in 6 cases, and no significant recovery in 2. The extent of the surgical resection was determined by the type of lesion; in more conservative resections which allowed for the reconstruction of tendinous insertions, the functional results were better than in wide resections. The difficulty of recovering good movement was related to the limited possibilities of reconstructing the insertions of the external rotator muscles.

Adult↗

Role of interleukin 2 (IL 2) and hemopoietin-1 (H-1) in the generation of mouse natural killer (NK) cells from primitive bone marrow precursors.

The development of natural killer (NK) cells from bone marrow (BM) precursors was studied. Recombinant interleukin 2 (IL 2) was able to induce the in vitro development of NK cells when added to cultures of mouse BM cells. Treatment of donor mice with 5-fluorouracil (150 mg/kg i.v.), which eliminates more differentiated cells but spares less differentiated cells, appears to augment NK cell development. The "NK stem cell" was found to be asialo GM1-, Thy-1+, Lyt-2-, and Lyt-1-. The cells generated in vitro had a typical phenotype of NK cells, being asialo GM1+, Lyt-5+, Thy-1+, Lyt-2-, and Lyt-1-. These effector cells also had specificity characteristics of NK cells lysing the NK-susceptible YAC-1 and K562 targets, but not the NK-resistant EL/4 or allogeneic and syngeneic blasts. Hemopoietin-1 (H-1), a factor which acts on very primitive multipotent BM cells, was able to cooperate with IL 2, increasing the development of NK cells. In contrast, other factors such as interleukin 3 or colony-stimulating factor did not cause induction of NK activity when added to cultures of BM cells, indicating that this effect, i.e., induction of NK cell development, is peculiar to IL 2. These results indicate that IL 2 can act as a differentiation as well as growth factor for NK cells, and that H-1 can promote the development of functional activity in a lymphocyte subpopulation as well as affect the differentiation of myelomonocytic and other cell lineages. This experimental system appears quite useful for characterization of BM precursors for NK cells, and should help to better understand the relationship of the NK cell lineage to the T cell or other lineages.

Animals↗

Effect of in vivo administration of prostaglandins and interferon on natural killer activity and on B-16 melanoma growth in mice.

We investigated the effect on in vivo administration of 16,16-dimethyl-prostaglandin E2 (di-M-PGE2) alone and in combined treatment with alpha-beta interferon (IFN) on NK activity in normal, cyclophosphamide (CY)-treated, tumor bearing or irradiated and bone marrow reconstituted mice and on B-16 melanoma growth. Normal mice inoculated with IFN (30,000 U/mouse, 24 hr before testing) showed a significant increase in NK activity, while those treated with di-M-PGE2 (10 micrograms/mouse daily X 4 days) showed a suppressed NK response. No difference was observed between mice treated with di-M-PGE2 alone and those treated with di-M-PGE2 associated with IFN. In immunosuppressed animals single treatments were slightly (di-M-PGE2) or not (IFN) effective, while the combined administration of di-M-PGE2 and IFN caused a marked increase in NK activity. Moreover, di-M-PGE2 was able to accelerate the recovery rate of NK activity in bone marrow-reconstituted murine chimeras, suggesting that the synergistic effect of prostaglandins and IFN could derive from the action of di-M-PGE2 on progenitor pre-NK cells and of IFN on effector cells. Finally, we observed a good correlation between the enhancement of the NK activity and the tumor growth inhibition.

16,16-Dimethylprostaglandin E2↗

Phenotypic and functional abnormalities of T lymphocytes in pathological hyperprolactinemia.

The phenotype and function of T cells circulating in patients with pathological hyperprolactinemia were analyzed and compared to those in sex- and age-matched control subjects. Two-color immunofluorescence study revealed an increased number of CD4+ TQ1+ cells and the presence of phenotypically immature CD1+ T cells, also exhibiting transferrin surface receptor, in peripheral blood of the hyperprolactinemic patients. After chronic treatment with the dopamine agonist bromocriptine, T-cell abnormalities disappeared. In addition, some untreated patients showed enhanced T-cell suppressor activity in an in vitro pokeweed mitogen-driven B-cell transformation assay. These immunological findings confirm a link between neuroendocrine and immune systems in humans.

Antigens, Differentiation, T-Lymphocyte↗

New heterocyclic derivatives of benzimidazole with germicidal activity. IV--In vivo anticandida activity of 5-fluoro-2-(5'-nitro-2'-furyl) benzimidazole (F-O-NO2).

We have studied the possible in vitro and in vivo antibacterial activity of 5-fluoro-2-(5'-nitro-2'-furyl)benzimidazole (F-O-NO2). Our data demonstrate that F-O-NO2 is able to inhibit the in vitro growth of different mycetes and bacteria, including Candida albicans and Cryptococcus neoformans. We also tested the possible in vivo activity against Candida albicans. The results clearly show that treatment with F-O-NO2 is able to significantly augment the survival of all treated animals; in particular, when injected i.p. at the dose of 120 mg/kg, 30' or 1 hr after Candida albicans challenge, it givens a MST (Medium Survival Time) longer than 60 days. These data demonstrate that F-O-NO2 has antibacterial and antimycotic activity.

Animals↗

Combined effects of immunity and antitumor drugs against cancer. I. In vivo studies with cis-diamminedichloroplatinum and cyclophosphamide in mouse models.

Cis-diamminedichloroplatinum (DDP) or cyclophosphamide (Cy) were given to mice bearing L1210 or LSTRA leukemia in H-2 compatible tumor-host combinations. Little anti-tumor activity was afforded by DDP against both leukemias inoculated in entirely histocompatible recipients. However, when the drug was given to mice incompatible for minor histocompatibility loci (MMHL) with the tumor, the efficacy of the treatment was markedly augmented and a substantial number of long-term survivors was found among BALB/c mice inoculated with L1210 cells. On the other hand, no difference in survival times was found between histocompatible or allogeneic mice inoculated with both leukemias, not subjected to chemotherapy. The LSTRA model was much less susceptible to this type of DDP-mediated antineoplastic immuno-chemotherapy synergism. Moreover no synergistic effects with allograft reaction were detected with Cy in both L1210 and LSTRA models, although Cy was markedly more active than DDP against leukemic cells in histocompatible recipients.

Animals↗

Interleukin-1 augments the interleukin-2-dependent generation of natural killer cells from bone marrow precursors.

We have studied the possible role of interleukin-1 (IL-1) on the interleukin-2 (IL-2) dependent development of mouse natural killer (NK) cells from primitive bone marrow (BM) precursors. Results indicate that both IL-1 alpha and IL-1 beta (1-10 U/ml) are able to stimulate the generation of NK cells from 5-fluorouracil (5-FU) resistant BM progenitors. These precursor cells are asialoGM1-, Thy-1+, Lyt-1- and Lyt-2-. Effector cells generated by culturing with IL-2 (40 U/ml) and IL-1 (5 U/ml) are Thy-1+, asialoGM1+, Lyt-5+, Lyt-1-, Lyt-2- and lyse only NK-susceptible targets. Generation of NK cells is blocked by addition of anti-IL-2/r. These data indicate that IL-1 may play a role in the generation of mature NK cells from undifferentiated BM precursors.

Animals↗

The medium-term results of cementless Lord-type hip prosthesis.

The results of 58 cementless total hip prostheses (Lord madreporous type) were evaluated 4 to 7 years after implantation. The functional results were generally satisfactory, although in approximately half the cases some pain was still present. Radiographic examination allowed us to analyse the response of the diaphyseal bone to the different situations of the endomedullary implant. Acetabular wear, which is one of the factors which may influence the long-term results, was also evaluated.

Bone Cements↗

Variations in alpha-2-HS glycoprotein level in neoplastic disease with and without involvement of bone.

Variations in the serum level of alpha-HS-glycoprotein may be observed in all pathological conditions which induce changes in bone turn-over, as well as in inflammatory and neoplastic diseases. This study includes 162 patients divided into four groups according to the TNM classification (tumour, lymph node metastasis). The first consisted of patients with neoplasms at TNM stages 1 and 2 with no bone metastases; the second of similar patients at TNM stages 3 and 4. The third group were patients with primary or secondary neoplasms of bone, and the fourth were patients with viral or bacterial diseases. The levels of alpha-2-HS-glycoprotein serum were determined for all the groups and these were compared with AAG (alpha-1-glycoprotein) and CEA (carcinoembryonic antigen). There were no significant differences in the levels of alpha-2-HS-glycoprotein for the first group as compared with normal controls, while in the other groups the differences were significant. The levels of alpha-2-HS-glycoprotein were diminished when the levels of CEA and AAG were both high, but increased when only one of these other parameters was high.

Adult↗

Generation of mouse natural killer (NK) cell activity: effect of interleukin-2 (IL-2) and interferon (IFN) on the in vivo development of natural killer cells from bone marrow (BM) progenitor cells.

The possible effect of IL-2, alpha,beta-IFN and poly I:C (an IFN inducer) administration on the generation of NK cells of LI and BM-reconstituted animals was investigated. B6D2F1 mice were LI (9.5 Gy) by total-body irradiation and reconstituted by i.v. injection of different doses (ranging from 10(6) to 2 X 10(7)) of syngeneic BM, after which the levels of splenic NK activity were evaluated on days 4, 7, 9, 12 and 14 after LI and BM graft. After a marked decline on day 4 (no detectable NK activity at any effector to target ratio tested), NK activity gradually returned, reaching the levels of untreated controls on day 9. Groups of LI and BM-reconstituted mice were also treated i.p. with mouse or human recombinant IL-2 from day 0 through day 3 (15-50 U/day/mouse) after BM transplantation. It appears that an earlier reconstitution of NK activity occurs in IL-2-treated animals as compared to medium-injected controls. LI and BM-reconstituted animals were also treated i.p. with alpha,beta-IFN (10(4) U/mouse) or Poly I:C (1 mg/kg/mouse) from day 0 through day 3, and the splenic NK activity was evaluated at 4, 7, 9, 12 and 14 days after LI and BM graft. Our data indicate that in vivo administration of IFN or Poly I:C was able to cause an earlier maturation of NK activity as measured on days 7 and 9 after LI. In contrast, when the NK activity of IFN-treated animals was compared with that of controls 14 days after LI and BM graft, a significant inhibition was found due to the induction of suppressor cells. Pre-treatment of donor BM with Poly I:C or IFN was also able to induce a more rapid reconstitution of NK activity of recipient mice. The NK activity reconstitution paralleled the increase in the number of splenic LGL. A synergistic effect was obtained when LI mice were transplanted with Poly I:C-pre-treated BM and then treated with IL-2. The effector cell in the IFN and IL-2 treated chimeras is a typical NK cell: asialo GM-1+, Thy 1 +/-, Lyt 1-, Lyt 2- and reactive only against NK-susceptible targets. These data suggest that IL-2 as well as IFN may represent maturational signals in the in vivo physiological regulation of growth and differentiation of BM NK stem-cells.

Animals↗

Low frequency of NK-cell progenitors and development of suppressor cells in IL-2-dependent cultures of spleen cells from low NK-reactive SJL/J mice.

Studies were performed to determine the basis for low NK activity in the spleens of SJL/J mice. In contrast to substantial boosting by IL-2 or IFN of NK activity of spleen cells from high NK-reactive strains of mice, no detectable effect of these cytokines on SJL spleen cells was seen. When SJL spleen cells were cultured for 7 days in the presence of IL-2, the frequency of proliferating cells was comparable to that of other strains of mice. However, the SJL spleen cells showed a frequency of NK-cell progenitors which was at least 50 times lower than that of the CBA/J spleen cells. In addition to having no detectable effector-cell activity, the cultures of SJL spleen cells contained suppressor cells which were able to inhibit the NK activity of spleen cells from other strains of mice. These suppressor cells did not adhere to plastic or nylon wool and were found in low-density fractions after Percoll density gradient centrifugation. The cultured SJL spleen cells had a high percentage of cells capable of binding to NK-susceptible target cells, which was similar to that seen in lytic cultures from other strains of mice. Thus, the suppressor activity may be attributable to competitive inhibition of the interaction of effector cells with target cells. Although several of the characteristics of suppressor cells were similar to those of cultured effector cells, they may not represent inactive or pre-NK cells since their progenitors were Thy1+ and AsialoGM1- whereas the progenitors of cultured effector cells in high NK strains were Thy1- and GM1+. The ability to eliminate the progenitors of the suppressor cells by pretreatment of spleen cells with anti-Thy1 plus C' also suggested that the low or undetectable NK activity of the cultured SJL cells is not attributable to suppression but may be due to an inherent deficit of NK cells.

Animals↗