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Biomedical subjects

A Facchini

Publications and source records attributed to A Facchini.

At least 55 records · Page 3Linked to original sources
PubMed2000

Effect of micronutrient status on natural killer cell immune function in healthy free-living subjects aged >/=90 y.

BACKGROUND: Natural killer (NK) cells play a role in natural immunity against tumor and infected cells. Advanced aging is associated with functional impairment of NK cells and increased susceptibility to nutritional deficiencies. OBJECTIVE: Our objective was to test whether micronutrient status affects NK cell activity in an older population. DESIGN: The relations between NK cell variables (percentage of leukocytes and cytotoxicity) and blood concentrations of selected micronutrients were studied in 62 healthy, free-living northern Italian subjects (25 men, 37 women) aged 90-106 y. Anthropometric measurements were also made. RESULTS: All subjects were well nourished according to age-specific anthropometric norms but many of them had micronutrient deficiencies. The prevalence of micronutrient deficiency was highest for selenium (in approximately 50% of both sexes), zinc (in 52% of men and 41% of women), and vitamin B-6 (in 40% of men and 59% of women), followed by vitamin A (in 16% of men and 27% of women) and vitamin E, vitamin B-12, and folate (each in <10% of both sexes). Ubiquinone-10 status was inadequate in 40% of women and 24% of men (P = 0.02). The percentage of NK cells was associated with serum zinc (men: r = 0.573, P = 0. 007; women: r = 0.373, P = 0.031) and selenium (women: r = 0.409, P = 0.018) concentrations. In women only, NK cell cytotoxicity at different effector-target cell ratios was positively associated with plasma vitamin E and ubiquinone-10 concentrations (P < 0.05). No significant associations with NK cell variables were found for the other measured nutrients. CONCLUSIONS: The results of this study strengthen the hypothesis that individual micronutrients may affect the number and function of NK cells in old age. The study also confirms the high prevalence of micronutrient deficiencies in healthy and apparently well-nourished persons aged >/=90 y.

Adult↗
PubMed2000

Increased risk of fibrosing alveolitis associated with interleukin-1 receptor antagonist and tumor necrosis factor-alpha gene polymorphisms.

Fibrosing alveolitis (FA) is characterized by persistent inflammation and elevated production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta), and interleukin-1 receptor antagonist (IL-1ra) in the lung. Single base variations at position +2018 in the IL-1ra gene (IL-1RN) and position -308 in the TNF-alpha gene (TNF-A) are overrepresented in other chronic inflammatory disease populations. We have tested the hypothesis that predisposition to FA may also be influenced by these polymorphisms by genotyping 88 cases and matched controls from England and 61 cases and 103 unmatched controls from Italy. The rarer allele for IL-1RN and TNF-A was designated allele 2 in each case. For IL-1RN allele 2, in the English group, the relative odds of FA were increased in homozygous subjects by an odds ratio (OR) of 10.2 (95% confidence intervals [CI], 1.26 to 81.4; p = 0.03) and for carriers by an OR of 1.85 (95% CI, 0.94 to 3.63; p = 0.075). In the Italian population, the risk of FA was increased, in IL-1RN allele 2 homozygotes (OR, 2.54; 95% CI, 0.68 to 9.50; p = 0.2) and in carriers (OR 2.40; 95% CI, 1.26 to 4.60; p = 0.008). Carriage of TNF-A allele 2 was also associated with increased risk of FA in the English (OR, 1.85; 95% CI, 0.94 to 3.63; p = 0.075) and Italian (OR, 2.50; 95% CI, 1.14 to 5.47; p = 0.022) populations. These data suggest IL-1RN (+2018) allele 2 and TNF-A (-308) allele 2 confer increased risk of developing FA and, therefore, that unopposed IL-1beta and/or excessive TNF-alpha may play a pathophysiologic role in this condition.

Aged↗
PubMed1999

Flow cytometric analysis of intracellular chemokines in chondrocytes in vivo: constitutive expression and enhancement in osteoarthritis and rheumatoid arthritis.

Chemokines play a key role in modulating leukocyte functions at sites of inflammation. To assess chondrocyte contribution to the chemotactic environment of inflamed joints the intracellular content of CC and CXC chemokines was investigated. IL-8, GROalpha, MCP-1, RANTES, MIP-1alpha and MIP-1beta expression was evaluated by flow cytometric analysis and RT-PCR in chondrocytes isolated from cartilage specimens obtained from patients with osteoarthritis and rheumatoid arthritis and multiorgan donors as normal controls. All the chemokines except RANTES were found in normal chondrocytes, with different degrees of staining intensity. In osteoarthritis and rheumatoid arthritis patients, an enhancement of IL-8, GROalpha, MIP-1alpha and MIP-1beta was observed.

Adult↗
PubMed1999

p44/42 mitogen-activated protein kinase is involved in the expression of ornithine decarboxylase in leukaemia L1210 cells.

The involvement of p44/42 mitogen-activated protein kinase (MAPK) in the induction of ornithine decarboxylase (ODC) was investigated by using PD98059, a specific MAPK-kinase (MEK1/2) inhibitor, and other signal-transduction inhibitors. In d,l-alpha-difluoromethylornithine (DFMO)-resistant L1210 cells stimulated to grow from quiescence, treatment with PD98059 inhibited p44/42 MAPK phosphorylation and the induction of ODC activity and protein. A marked reduction of the accumulation of mature ODC mRNA and its intron-containing precursor was observed, whereas ODC turnover was hardly affected. PD98059 also reduced the content of antizyme, but not that of antizyme mRNA. U0126, a novel and more potent inhibitor of MEK1/2, provoked a dose-dependent inhibition of ODC induction at lower concentrations with respect to PD98059. Other effective inhibitors of ODC induction proved to be genistein, manumycin A, herbimycin A, LY294002, wortmannin and KT5823, suggesting the involvement of other key proteins of signal-transduction pathways, i.e. Ras, Src, phosphatidylinositol 3-kinase and cGMP-dependent protein kinase, which may have a positive impact on MAPK. Cells kept in a DFMO-free medium, and thus containing high levels of putrescine and spermidine, showed enhanced MAPK phosphorylation and lower sensitivity to PD98059, compared with cells maintained in the presence of DFMO. In conclusion, these results indicate that the activation of p44/42 MAPK may favour the expression of ODC, and that polyamines, in turn, may affect the phosphorylation state of MAPK.

Animals↗
PubMed1999

Vitamin D, thyroid hormones and muscle mass influence natural killer (NK) innate immunity in healthy nonagenarians and centenarians.

Increasing evidence has demonstrated that the immune system closely interacts with other physiological systems, whose communications are mediated by circulating cytokines and hormones. The aim of our study was to test whether the number and cytolytic activity of NK cells in a group of relatively healthy Italian nonagenarians and centenarians were affected by the modifications of endocrine, metabolic and functional parameters that occur during ageing. Because of the extreme age of the study population, a cross-sectional analysis was performed. This study revealed that the group of oldest subjects with the highest number of NK cells and the best preserved cytolytic function also presented a preserved metabolism of thyroid hormones and vitamin D and integrity of muscle mass. In fact, the NK cell number and/or cytolytic activity of healthy subjects > 90 years old was positively associated with serum levels of vitamin D, while T3, FT4, i-PTH hormones and lean body mass were associated only with NK cell number. In conclusion, our results stress the paramount importance of nutritional evaluation in the clinical assessment of elderly people.

Activities of Daily Living↗
PubMed1999

A mathematical model predicting anti-hepatitis B virus surface antigen (HBs) decay after vaccination against hepatitis B.

The determination of serum levels of antibodies against hepatitis B virus surface antigen (anti-HBs) after hepatitis B vaccination is currently the only simple test available to predict the decay of protection and to plan the administration of booster doses. A total of 3085 vaccine recipients of plasma-derived and recombinant vaccine have been followed for 10 years to determine the kinetics of anti-HBs production and to construct a mathematical model which could efficiently predict the anti-HBs level decline. The anti-HBs peak level was reached 68 days after the last dose of recombinant vaccine and 138 days after the last dose of plasma-derived vaccines. The age of vaccinees negatively influenced the anti-HBs levels and also the time necessary to reach the anti-HBs peak. A bilogarithmic mathematical model (log10 level, log10 time) of anti-HBs decay has been constructed on a sample of recombinant vaccine recipients and subsequently validated on different samples of recombinant or plasma-derived vaccine recipients. Age, gender, type of vaccine (recombinant or plasma-derived), number of vaccine doses (three or four) did not influence the mathematical model of antibody decay. The program can be downloaded at the site: http:@www2.stat.unibo.it/palareti/vaccine.htm . Introducing an anti-HBs determination obtained after the peak, the program calculates a prediction of individual anti-HBs decline and allows planning of an efficient booster policy.

Algorithms↗
PubMed1999

Chemokine expression by subchondral bone marrow stromal cells isolated from osteoarthritis (OA) and rheumatoid arthritis (RA) patients.

We analysed the spontaneous and cytokine-stimulated production and expression in vitro of IL-8, GROalpha, MCP-1, RANTES, MIP-1alpha, MIP-1beta, by subchondral bone marrow stromal cells (BMSC) isolated from RA, OA, post-traumatic (PT) patients and normal donors (ND). BMSC were cultured in vitro in the presence or absence of IL-1beta and tumour necrosis factor-alpha (TNF-alpha), and assessed for chemokine production, expression and immunolocalization. BMSC from different sources constitutively released MCP-1, GROalpha and IL-8, but not MIP-1alpha or MIP-1beta, while BMSC from ND constitutively released only IL-8 and MCP-1. IL-8, GROalpha and RANTES production in basal conditions was significantly higher in RA patients than in ND. RANTES production was also higher in OA and RA than in PT patients. The combination of TNF-alpha and IL-1beta synergistically increased the production of all chemokines tested except for RANTES. Reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated that all chemokines not detectable in the supernatants were expressed at the mRNA level. Chemokine immunostaining was localized around the nuclei. This work demonstrates that BMSC from subchondral bone produce chemokines and indicates that these cells could actively participate in the mechanisms directly or indirectly causing cartilage destruction and bone remodelling.

Adult↗
PubMed1999

NK binding capacity and lytic activity depend on the expression of ICAM-1 on target bone tumours.

Osteosarcoma cell lines are differently lysed by natural killer (NK) lymphocytes. A critical step in the lytic process is the recognition and attachment of effector to target cells. To determine binding capacity and lytic activity of NK cells, we investigated the distribution and role of ICAM-1, 2 and 3 on two osteosarcoma cell lines (HOS and Saos-2) in basal conditions and after TNFalpha treatment. Modulation of ICAM-1 after TNFalpha treatment modified the binding capacity of NK cells to osteosarcoma target cells. This modulation process appears to play a critical role in determining the susceptibility of these cells to NK-mediated lysis.

Antigens, CD↗
PubMed1999

Proinflammatory cytokines and chemokine production and expression by human osteoblasts isolated from patients with rheumatoid arthritis and osteoarthritis.

OBJECTIVE: To evaluate whether subchondral osteoblasts (OB) are involved in the production of cytokines and chemokines in rheumatic diseases. METHODS: OB were isolated from subchondral bone of rheumatoid arthritis (RA), osteoarthritis (OA) and post-traumatic (PT) patients, cultured in vitro in the presence or absence of interleukin 1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), and assessed for the production, immunolocalization, and mRNA expression of proinflammatory cytokines (IL-1alpha, IL-1beta, TNF-alpha) and alpha and beta chemokines [IL-8, growth related gene product (GRO-alpha), monocyte chemoattractant protein 1 (MCP-1), RANTES, and macrophage inflammatory proteins MIP-1alpha, MIP-1beta]. RESULTS: Cultured OB from different patients did not release IL-1alpha, IL-1beta, or TNF-alpha, and constitutively secreted IL-8, GRO-alpha, and MCP-1, while RANTES, MIP-1alpha, MIP-1beta were undetectable or near the lower level of sensitivity of the immunoenzymatic assay. GRO-alpha was significantly higher in RA than in OA and PT patients. IL-1beta and TNF-alpha alone or in combination strongly stimulated chemokine release by OB. Only RANTES production was not increased by the combination of the 2 cytokines. IL-1alpha, IL-1beta, and TNF-alpha were expressed as cytoplasmic proteins and were not secreted by OB even after stimulation. CONCLUSION: OB from subchondral bone release chemokines that could be involved in the mechanisms that directly or indirectly cause bone remodelling and cartilage destruction.

Aged↗
PubMed1999

Chemokine production by human chondrocytes.

OBJECTIVE: To evaluate the role of chondrocytes in producing CXC chemokines [interleukin 8 (IL-8), growth related gene product (GRO-alpha)] and CC chemokines [monocyte chemoattractant protein (MCP-1), macrophage inflammatory protein (MIP-1alpha), RANTES] in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and subjects after traumatic injury (PT). METHODS: Articular cartilage specimens were obtained from 38 patients with OA and 18 with RA undergoing joint replacement surgery. Healthy human cartilage was obtained from femoral condyles removed after trauma in 11 subjects with no history of joint pathology (PT cases). Chondrocytes were isolated from articular cartilage by sequential enzymatic digestion and cultured in vitro. Chemokine production was investigated in unstimulated condition and after 72 h incubation with proinflammatory [IL-1beta, tumor necrosis factor-alpha (TNF-alpha)] and antiinflammatory [transforming growth factor-beta1 (TGF-beta1), IL-10] mediators. Chemokine concentrations in cell supernatants were evaluated by ELISA. RESULTS: Chondrocytes produce all these chemokines to a different extent. IL-1beta was a more potent stimulus than TNF-alpha in inducing production of all chemokines except MCP-1. We found no statistical differences among chondrocytes isolated from OA, RA, and PT for chemokine production in either basal conditions or after cytokine stimulation. IL-1beta induced chemokine production can be modulated by TGF-beta1 in different ways according to the various chemokines, while IL-10 does not affect IL-1beta induced chemokine production. CONCLUSION: Chondrocytes produce IL-8, GRO-alpha, MCP-1, MIP-1alpha, and RANTES. Proinflammatory factors (IL-1beta, TNF-alpha) effectively upregulate chemokine production, but production is scarcely modulated by the antiinflammatory mediators TGF-beta and IL-10. Chondrocyte derived chemokines may play a role in triggering the mechanisms involved in pathogenesis and persistence of joint diseases.

Adult↗
PubMed1998

Spermine causes caspase activation in leukaemia cells.

Exposure of several leukaemia cell types to the polyamine spermine triggered caspase activation. In HL60 cells, the onset of caspase activity correlated with the accumulation of spermine, and was accompanied by the processing of the caspase-3 precursor and the digestion of the substrate proteins PARP and gelsolin. Spermine also induced the accumulation of cytochrome c in the cytosol. Caspase activation triggered by spermine was not blocked by antioxidants or inhibition of polyamine oxidase. The deregulation of polyamine uptake strongly sensitised the cells to spermine-induced caspase activation. These data show that an excessive intracellular level of spermine triggers caspase activation that is not mediated by oxidative mechanisms, and suggest a model where elevated free cytosolic polyamines may act as transducers of a death message.

Animals↗
PubMed1998

Psychosocial integration of adolescents and young adults with thalassemia major.

UNLABELLED: The aim of this study was to explore the effect of thalassemia major on the psychosocial adjustment of adolescents and young adults. DESIGN: unmarried adolescent and young adult patients were asked to fill in an ad hoc questionnaire; a semi-structured interview exploring marriage and family life was done with married patients. SAMPLE: group A: 90 unmarried patients, 50% females and 50% males, aged 14-22 years. The control group was formed by 100 matched subjects; group B: 19 thalassemic married subjects, 6 males and 13 females, aged 28-45 years, 7 patients had children and 12 did not. RESULTS: group A: subjects with thalassemia had normal psychological and social development and scored better than their normal peers in tests investigating social adjustment, self-esteem and self-description. Moreover the family relationships of adolescents with thalassemia appeared to be stronger than those reported by normal controls; group B: the behavior of thalassemic couples did not differ from the one observed in non-thalassemic couples in the course of previous investigations. CONCLUSIONS: Our data shows that neither thalassemic adolescents nor thalassemic married, well-treated, young adults differ significantly from the healthy young people in their ability to cope with life's difficulties both in adolescence and marital life.

Adaptation, Psychological↗
PubMed1998

Natural immunity and bone and muscle remodelling hormones in the elderly.

Increasing evidence has demonstrated that the immune system is closely integrated with two other physiological systems: endocrine and nervous. They communicate through circulating humoral factors such as cytokines, hormones and neurotransmitters. We undertook a cross-sectional analysis in a group of elderly subjects over 90 years to demonstrate that a functional relationship exists among the number and cytolytic activities of NK cells, bone and muscle remodelling hormones, anthropometric parameters and physical ability. Peripheral blood samples collected from 62, 90-106 years-old subjects underwent biochemical (bone and muscle remodelling hormone levels) and immunological determinations (Natural Killer cell distribution and activity), anthropometric and functional assessment. Significant associations were found among NK cell number and cytolytic activity and serum concentrations of vitamin D, anthropometric parameters, while functional independence in daily activity was only associated with NK cell number. In general a high level of physical ability was correlated with preserved body stores and vitamin D levels. In conclusion, our results stress the importance of nutritional evaluation in the clinical assessment of elderly people. The magnitude of the NK immune response, which constitutes the first line of defence against infected and neoplastic cells, is best preserved in oldest-old people with the best hormonal parameters and nutritional measures.

Aged↗
PubMed1998

Enhanced and coordinated in vivo expression of inflammatory cytokines and nitric oxide synthase by chondrocytes from patients with osteoarthritis.

OBJECTIVE: To evaluate the sites of expression of interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNFalpha), and inducible nitric oxide synthase (iNOS) in patients with inflammatory and degenerative joint diseases. METHODS: Cytokines and iNOS were detected by immunohistochemistry analysis of synovial and cartilage biopsy specimens obtained at knee arthroscopy in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), osteoarthritis (OA), and traumatic knee arthritis. Cytokine and iNOS expression was quantified using computerized image analysis. RESULTS: IL-1beta, TNFalpha, and iNOS were highly expressed by synovial cells (lining layer cells, infiltrating leukocytes, endothelial cells) from patients with inflammatory arthritides and significantly less by synovial cells from patients with OA and traumatic arthritis. In contrast, the latter patients showed high chondrocyte expression of cytokines and iNOS while RA and PsA patients had only minor chondrocyte positivity. In both joint compartments, IL-1beta expression, TNFalpha expression, and iNOS expression were strongly correlated. CONCLUSION: The enhanced and coordinated expression of IL-1beta, TNFalpha, and iNOS by chondrocytes strongly supports the hypothesis that chondrocytes are the major site of production of mediators of inflammation in human OA, thus playing a primary role in the pathogenesis of this disease.

Adult↗
PubMed1998

Different pattern of cytokine production and mRNA expression by lymphoid and non-lymphoid cells isolated from human palatine tonsil.

To investigate the cytokines involved in the interaction between circulating (B and T lymphocytes) and non-circulating (stromal cells) elements present in lymphoid tissue, highly purified populations were isolated from human tonsils and the cytokine production and mRNA expression (interleukin-1 alpha, -2, -4, -5, -6, -8, -10, leukocyte inhibitory factor, granulocyte-macrophage colony-stimulating factor, and interferon-gamma) were assessed both by immunoassay and reverse transcriptase polymerase chain reaction under resting conditions and after activation with tumor necrosis factor-alpha. Under basal conditions most cytokines were not detected, except for interleukin-8 which was produced by T lymphocytes and lymphoid cells. Activation by tumor necrosis factor-alpha induced interleukin-8 production by B lymphocytes. Tonsillar T lymphocytes expressed mRNA for interleukin-1 alpha, -8, -10, -4, leukocyte inhibitory factor, and interferon-gamma, only interleukin-4 was expressed by resting peripheral blood T lymphocytes. Tonsillar B lymphocytes were mRNA positive for interleukin-1 alpha, -8, -10, leukocyte inhibitory factor, and interferon-gamma, these were not expressed by peripheral blood B lymphocytes. Stromal cells constitutively produce interleukin-6 whose levels increased 5 times upon tumor necrosis factor-alpha activation Granulocyte-macrophage colony-stimulating factor and interleukin-8 were detected only after tumor necrosis factor-alpha activation. Only stromal cells constitutively express interleukin-6 and granulocyte-macrophage colony-stimulating factor and show a cytokine pattern different from that described for other non-lymphoid cells, such as follicular dendritic cells. These data indicate that in the human tonsil population, lymphoid and non-lymphoid cells can be distinguished by different patterns of cytokine expression.

Child, Preschool↗
PubMed1998

Mapping of topoisomerase II alpha epitopes recognized by autoantibodies in idiopathic pulmonary fibrosis.

Autoantibodies against DNA topoisomerase II alpha have been identified in the sera of patients with idiopathic pulmonary fibrosis (IPF). To map topoisomerase II autoepitopes, we tested by ELISA and immunoblotting the IPF anti-topoisomerase II-positive sera against a series of recombinant proteins which covered the full length of topoisomerase II alpha. Specific patterns of reactivity were observed, indicating the existence of multiple epitopes on topoisomerase II, either highly complex or conformational/discontiguous or conformational/contiguous ones. The latter resided in amino acid residues 854-1147 and 1370-1447. A detailed analysis of these regions was undertaken, but we were not able to pinpoint a sequential peptide-sized epitope, or any significant homology with foreign pathogens. Further, we observed a significant correlation between the progression from a contiguous to a quaternary/tertiary structure-dependent autoepitope and the disease duration but not with the disease severity. Therefore, this result supports the hypothesis that anti-topoisomerase II autoreactivity evolves following an antigen-driven process.

Adult↗
PubMed1998

Age-dependent decreases of NK cell phosphoinositide turnover during spontaneous but not Fc-mediated cytolytic activity.

The progressive increase in the number of peripheral NK cells found in the elderly does not correlate with a corresponding increase in lytic activity. On the contrary, a decreased function of circulating NK cells purified from old subjects was observed on a per cell basis. Most of the studies on NK cells have focused on late events such as lytic activity. In view of this, little is currently known about the modification of the early signalling pathways of NK cells in elderly people. This study investigated whether the modification of NK lytic activity could be related to differences in the metabolic pattern of activation of these cells in the elderly. NK cells were negatively purified by immunomagnetic depletion from the peripheral blood of selected old and young healthy subjects. Hydrolysis of inositol phospholipids was measured following incubation with K562 target cells and/or CD16 mAb for different times. Our data show that there is a pronounced age-related decrease in the ability to generate total inositol monophosphates and, particularly, inositol trisphosphates by NK cells following K562 stimulation (spontaneous cytolytic activity) together with an attenuated and delayed hydrolysis of phosphatidylinositol bisphosphate, while phosphoinositide turnover is preserved following Fc triggering (antibody-dependent cell-mediated cytotoxicity). These results confirm that, also in old subjects, different biochemical pathways of activation are involved in NK cells when target or antibody-mediated triggering occurs and may aid the development of experimental and therapeutic strategies to counteract declines in cell mediated immune functions associated to advancing age.

Adult↗