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Biomedical subjects

A Angeli

Publications and source records attributed to A Angeli.

243 records · Page 14Linked to original sources
PubMedDate not supplied

[In vitro effects of peptides of the corticostatin/defensin family on production of mitogen-induced cytokines].

Cytokines are autocrine, paracrine and endocrine glycoproteins that interact with specific cell receptors and have pleiotropic effects. Increasing evidence indicates that cytokines, immune interferon (IFN-gamma) and interleukin 6 (IL-6) among others, modulate hypothalamic-pituitary-adrenal function. Corticostatins/defensins are a family of cationic peptides recently isolated from phagocytic cells of myeloid lineage. Four peptides have been isolated from human neutrophils: HP-1, 2, 3 and 4. As defensins they participate in immunosurveillance against viruses, bacteria and fungi. Some members of the family are also able to inhibit ACTH-induced steroidogenesis. Among human peptides, only HP-4 is corticostatic. We previously demonstrated that HP-1 and HP-4 inhibit in vitro the spontaneous and cytokine-inducible natural killer activity of human peripheral blood mononuclear cells (PBMC) and potentiate cortisol-dependent inhibition. The present work was carried out to determine whether two human corticostatins/defensins, HP-1 and HP-4, were able to modulate in vitro IFN-gamma and IL-6 production by human PBMC stimulated with phytohemagglutinin or Concanavalin A. IFN-gamma was titrated using biological assay with WISH cells as indicators and vesicular stomatitis virus as the challenge virus. IL-6 was measured by means of enzyme amplified sensitivity immunoassay. Both HP-1 and HP-4 significantly reduced cytokine production. Our data indicate that HP-1 and HP-4 are novel modulators of lymphocyte functions in vitro. Their depressing properties on ACTH-induced steroidogenesis and on cytokine production add complexity to neuroendocrine-immune circuits involving hypothalamic-pituitary-adrenal function.

Anti-Bacterial Agents↗
PubMedDate not supplied

High frequency of p53 expression in colo-rectal adenomatous polyps.

Previous studies on p53 protein expression in colonic adenomas showed controversial results. The present study evaluates the p53 expression in colonic adenomas, at different dysplasia degrees, by immunohistochemical analysis, using a newly introduced monoclonal anti-p53 antibody. Paraffin embedded sections of 48 colorectal adenomas, 5 colonic carcinomas and 11 normal colonic biopsies were studied by immunohistochemical analysis using a monoclonal mouse anti-p53 antibody (clone DO-1). Normal colonic mucosa specimens and 5/48 adenomas were found negative for p53 staining. p53-positive nuclei were less than 10% in 22/48 and between 10 and 40% in 15/48 adenomas. In 6/48 adenomas and in 4/5 carcinomas we found a high percentage of p53-positive nuclei (> 40%). Immunohistochemical p53-positivity is a common event in colonic adenomas, not dependent on dysplasia degree. It might be the result of p53 wild-type increase, due to the typical genomic instability of colonic adenomas.

Adenomatous Polyps↗
PubMedDate not supplied

Altered circadian rhythms of natural killer (NK) cell activity in patients with autoimmune rheumatic diseases.

Natural Killer (NK) cells are a lymphocyte subset actively involved in cytotoxicity against tumor-transformed and virus-infected cells; they are a reliable model for the study of neuroendocrine-immune interactions. In previous works we demonstrated that in healthy subjects NK activity of peripheral blood mononuclear cells (PBMC) and susceptibility to endogenous modifiers display statistically validated circadian rhythms. In rheumatoid arthritis (RA) and in other autoimmune rheumatic diseases abnormalities of the circadian rhythm of serum cortisol and altered levels of NK cell activity have been reported. We evaluated the circadian pattern of NK cell activity in 7 hospitalized patients with autoimmune rheumatic diseases (4 RA, 1 scleroderma, 2 mixed connective tissue disease). Temporal variations of in vitro responses to either positive recombinant (immune interferon, r IFN-gamma IFN-gamma: 650 IU/ml; recombinant interleukin-2, r IL-2 IL-2: 100 IU/ml) or negative (cortisol: 10(-6) M) modifiers were also studied. Blood was drawn at 4h intervals for 24 h, starting at 0800. PBMC preparations were immediately separated and incubated for 20h in the presence or absence of modifiers. NK activity was assessed with a direct non-radiometric 4h cytolytic assay, using K 562 cells as targets. Significant circadian variations of spontaneous NK activity were documented only in women with RA, with a peak in the evening hours and a minimum in the night or in the early morning (p < 0.05, PR 51.5%, phi 1829). Population-mean cosinor analysis did not yield detection of significant circadian variations of in vitro responsiveness to modifiers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Natural killer (NK) cell activity of women with gross cystic disease is inhibited in vitro by breast cyst fluid.

Gross cystic disease (GCD) represents an advanced form of fibrocystic disease of the breast. Bearers of macrocysts have been reported to be at risk of developing breast cancer. Natural killer (NK) cells are a lymphocyte subset deeply involved in immunosurveillance against neoplasia. We investigated whether breast cyst fluid (BCF) aspirated from patients with GCD could affect in vitro the spontaneous and lymphokine-inducible NK activity of peripheral blood mononuclear (PBM) cells concomitantly drawn from the same patients. PBM cells exposed to BCF were evaluated by a standard cytotoxic assay, using K562 cells as a target, in the presence or absence of lymphokines. In vitro incubation of PBM cells with BCF resulted in a consistent decrease of NK cell activity (mean level of suppression about 50%; p < 0.001). Furthermore, exposure of PBM cells to BCF completely prevented the IFN-gamma-dependent enhancement and consistently reduced the IL-2-induced NK activity (p < 0.01). The phenomenon was more apparent for type II cyst BCF. Our data are compatible with an immunosuppressive effect of BCF, potentially leading to altered "local immunosurveillance".

Aged↗
PubMedDate not supplied

[The autocrine-paracrine modulation of natural killer activity in man by peptides of the corticostatin-defensin family].

Corticostatins (CS)-defensins are a family of peptides recently isolated from neutrophils and cells of myeloid lineage. They have been termed CS in that members of the family inhibit ACTH-induced steroidogenesis, and defensins in that they are highly effective as enhancers of intracellular killing of pathogens. Natural killer (NK) cells are an immunocyte subset whose cytotoxic activity is modulated by lymphokines and hormones. Recent evidence suggests a myeloid origin for these cells. We evaluated whether two human CS-defensins, HP-1 and HP-4, are able to modulate in vitro spontaneous NK cell activity of human peripheral blood mononuclear (PBM) cells and in vitro susceptibility to the stimulatory effect by immune interferon (IFN-gamma) or interleukin 2 (IL-2) and to the inhibitory effect of cortisol. PBM cells were incubated for 20 h with HP-1 or HP-4 and IFN-gamma or IL-2 or cortisol. NK cell activity was measured in a 4-h direct cytotoxicity assay (K562 cells as a target). We also searched for CS-defensins in NK-enriched cell preparations by means of HPLC separation of the supernatant obtained from sonicated cells. HP-1 and HP-4 significantly inhibited both spontaneous and lymphokine-inducible NK cell activity, and potentiated cortisol-dependent inhibition. Radioimmunoassay on HPLC purified fractions demonstrated the presence of HP-1 in NK-enriched cell preparations. Our data indicate that HP-1 and HP-4 are negative modulators of NK cell cytotoxicity and that autocrine/paracrine mechanisms are conceivably involved. HP-1 production by NK cells may be viewed as additional support for the thesis of the myeloid origin of these immune effectors.

Blood Proteins↗
PubMedDate not supplied

Biochemical picture of bone metabolism in breast cancer patients with bone metastases.

A panel of bone turn-over markers was assessed in 75 normocalcemic patients bearing bone metastases from breast cancer (BC), and in 25 advanced/metastatic BC patients without clinical appearance of bone involvement. 115 healthy women, stratified in three subgroups according to age served as controls. Bone formation was investigated by measuring serum carboxyterminal propeptide of type I procollagen (PICP), Bone Gla Protein (BGP, osteocalcin), bone isoenzyme of alkaline phosphatase (BALP); bone resorption by measuring serum carboxyterminal telopeptide of type I collagen (ICTP), fasting urinary hydroxyproline/creatinine (OHPro/Cr) and calcium/creatinine (Ca/Cr). In patients with bone metastases the percent of supranormal values (higher than mean plus 2 SD of the age-matched controls) ranged between 25% and 40% for indices of bone formation, about 73% for both ICTP and OHPro/Cr and about 30% for Ca/Cr. The median levels of all bone turn-over markers were higher in bone metastatic patients than in those without apparent skeletal involvement, but significance was attained only for OHPro/Cr, Ca/Cr and BALP. Supranormal levels of ICTP and OHPro/Cr were also found in about 65-70% of patients without apparent skeletal involvement. ICTP and Ca/Cr significantly correlated with bone pain score, BALP, ICTP, Ca/Cr significantly correlated with the number of tumour appearances in bone. In conclusion, the bone resorption indices, ICTP and OHPro/Cr, are much more frequently elevated than bone formation indices in BC patients with or without skeletal involvement. Their potential use in the early detection of bone metastases is hampered by the insufficient knowledge on specificity. Among the biochemical markers evaluated, Ca/Cr, ICTP and BALP, due to correlation with clinical aspects, appear the most interesting for follow-up studies.

Adult↗
PubMedDate not supplied

Differential integrin expression in thyroid and laryngeal carcinomas.

Several laryngeal and thyroid carcinomas were studied immunohistochemically to evaluate whether the expression and distribution of integrins and basal lamina components can represent reproducible markers for correct early diagnosis and prognosis. In laryngeal cancers, the depolarization and pericellular redistribution of alpha 3 beta 1 and alpha 6 beta 4, and focal or massive fragmentation of the basal lamina, according to tumor prognosis, occurred. In thyroid carcinomas, loss of polar topography of alpha 3 beta 1 and neo-expression of alpha 6 beta 4 in histopathologically or clinically aggressive cancers were observed. Therefore, the addition of a panel of adhesion molecules to the toolbox of surgical pathologists may improve diagnostic and prognostic procedures.

Adult↗
PubMedDate not supplied

Osteoblastic flare assessed by serum alkaline phosphatase activity is an index of short duration of response in prostate cancer patients with bone metastases submitted to systemic therapy.Gruppo Onco Urologico Piemontese (G.O.U.P).

A transient rise in serum alkaline phosphatase (ALP) activity (ALP flare) after androgen deprivation in prostate cancer patients with bone metastases has been previously correlated with both response to therapy and poor prognosis. In the present study we analyzed data coming from an Italian multicenter phase III, trial aimed to compare the efficacy of treatment with goserelin alone with that of goserelin plus mitomycin C. Sixty-seven bone metastatic patients were enrolled: 32 were treated with goserelin and 35 with and goserelin plus mitomycin. 58 cases had ALP measured every month; and were considered for flare assessment. Remarkably elevated ALP and PSA levels at baseline were significantly correlated with poor prognosis. The addition of mitomycin to goserelin resulted in a greater percent reduction of PSA values with respect to goserelin alone but did not augment the time to progression and overall survival. The monthly profile of ALP serum levels was superimposable in patients assigned to hormone therapy or chemotherapy plus hormone therapy. Patients showing a flare in ALP activity (transient rise > 15% in ALP values with respect to baseline at the first month) were classified as responders to therapy or as having stable disease upon PSA evaluation and/or at bone pain assessment, but had a shorter time to progression (median 12 months) in comparison to those showing a different ALP pattern (median 23 months). The measurement of flare in ALP activity during androgen suppression with or without concomitant mitomycin administration, may permit the early identification of patients who are likely to progress rapidly, and hence be candidate for more aggressive treatments.

Aged↗