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Biomedical subjects

S Bernasconi

Publications and source records attributed to S Bernasconi.

At least 91 records · Page 5Linked to original sources

[An assessment of abdominal fatty tissue distribution in obese children. A comparison between echography and computed tomography].

PURPOSE: Computed tomography (CT) and, more recently, ultrasound (US), have proved excellent tools for quantifying adipose tissue distribution. Body fat distribution is an important factor in the treatment of obesity and its complications. We investigated the correlation between CT and US measurements in pediatric obesity. MATERIAL AND METHODS: Forty obese children and adolescents aged 4.1-14.8 years were submitted to CT and US. Intra-abdominal, subcutaneous and total body fat were calculated (in cm2), with the CT image analysis software. The rectus muscle-spine and rectus muscle-aorta distances, as indicative of visceral fat thickness, were measured on US images with(out) compression. The distance between skin-fat and fat-rectus muscle interfaces was measured as subcutaneous fat thickness. We also compared US-CT findings with other morphometric variables--i.e., patient's (ideal) body weight and skin fold measures. RESULTS: At US, the rectus muscle-aorta and rectus muscle-spine distances ranged 2.4-7.5 cm (mean: 4.47 cm) and 3.6-8.9 cm (mean: 5.79 cm), respectively. The skin-rectus muscle distance ranged 1.2-7.5 cm (mean: 3.14 cm). A statistically significant correlation was found between the CT measurement of visceral fat and the aorta-rectus muscle and rectus muscle-spine distances (r = 0.80 and 0.74, respectively). The US measurements of subcutaneous fat were correlated with CT subcutaneous fat area (r = 0.82). No correlation was found between overweight, as calculated by body mass index, and CT or US fat. CONCLUSION: Our findings indicate that US is as useful as CT in evaluating body fat distribution in pediatric obesity.

Abdomen↗

Oral health in children and adolescents with IDDM--a review.

Children with insulin-dependent diabetes mellitus have a lower salivary flow rate, pH and buffer capacity, but a higher glucose content and peroxidase, IgA, magnesium and calcium concentration, in comparison with healthy children. Nevertheless the incidence of caries is lower than normal in diabetic children with good metabolic control. Periodontal disease usually starts at puberty as mild gingivitis with bleeding and gingival recession, and it may develop into severe periodontitis, especially in children with poor control of diabetes. Microangiopathy, impaired immune response, different bacterial microflora and collagen metabolism are involved in the pathogenesis of diabetic periodontal disease. The gingival flora is mostly composed of Gram-negative, anaerobic bacteria, while collagen has a lower solubility and is atrophic and inadequate to support the occlusion forces. For these reasons, prevention of periodontitis is important in diabetic children; they should receive oral hygiene instruction and visit a dentist at least twice a year.

Adolescent↗

Interleukin 8 and monocyte chemoattractant protein-1 in patients with juvenile rheumatoid arthritis. Relation to onset types, disease activity, and synovial fluid leukocytes.

OBJECTIVE: To measure serum and synovial fluid (SF) levels of interleukin 8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) in patients with juvenile rheumatoid arthritis (JRA) and to compare them with adult rheumatoid factor-positive rheumatoid arthritis (RA). METHODS: IL-8 and MCP-1 were measured by immunoassay (1) in sera obtained from 55 children with JRA and from 16 adults with RA, and (2) in SF obtained from 30 children with JRA and 11 adults with RA. RESULTS: Patients with active systemic JRA had serum levels of IL-8 and MCP-1 higher than in controls (p<0.01) and in patients with active polyarticular or pauciarticular JRA (p<0.05). In patients with RA serum MCP-1 levels were higher than in patients with the 3 JRA onset types, while no difference was found for IL-8 levels. Patients with systemic JRA and with current systemic features had serum levels of IL-8 and MCP-1 higher (p = 0.03 and p = 0.04, respectively) than patients in which systemic features had subsided. No significant differences in SF IL-8 or MCP-1 levels were found among the 3 JRA onset types or adults with RA. In patients with JRA SF leukocyte counts were correlated with SF IL-8 levels (p = 0.002), but not with MCP-1 levels. Moreover, SF levels of both IL-8 and MCP-1 were correlated with those of IL-1beta (p<0.001) and IL-6 (p<0.01), but not with those of TNF-alpha. CONCLUSION: Elevated serum levels of IL-8 and MCP-1 in patients with systemic JRA with current systemic features at sampling suggest systemic production of the 2 chemokines during systemic phases of the disease. Similar SF levels of IL-8 and MCP-1 among the 3 JRA onset-types and RA suggest comparable local production of the 2 chemokines.

Adolescent↗

Adhesion, transendothelial migration, and reverse transmigration of in vitro cultured dendritic cells.

Dendritic cells (DC) are migratory cells which exhibit complex trafficking properties in vivo, involving interaction with vascular and lymphatic endothelium and extracellular matrix (ECM). The underlying mechanisms involved in these processes are still ill defined. In the present study we have investigated the ability of DC to interact in vitro with human vascular endothelial cells (EC) and ECM. DC were differentiated from monocytes by in vitro exposure to granulocyte-macrophage colony-stimulating factor and interleukin-13 for 7 days. In adhesion assays a considerable proportion of DC bound to resting EC monolayers: (17% +/- 4%, mean +/- SE of eight experiments). Adhesion to tumor necrosis factor (TNF)-activated EC was increased to 29% +/- 5% (n = 8). Binding to resting EC was strongly inhibited by anti-CD11a and CD11b, but not by CD11c monoclonal antibodies (MoAbs); on TNF-activated EC, anti-VLA-4 in concert with anti-CD18 inhibited adhesion by more than 70%. Binding to a natural ECM, derived from cultured EC, or to purified fibronectin was high: 52% +/- 6% (n = 8) involved VLA-4 and VLA-5 integrins. In a transmigration assay, 10% +/- 2% (n = 6) of input cells were able to cross the EC monolayer. Unlike adhesion, transendothelial migration was significantly reduced by anti-CD31 MoAb. The amount of DC transmigrated through a monolayer of EC was increased twofold to threefold by a defined set of C-C chemokines including RANTES, MIP1alpha, MIP5, and, to a lesser extent, by MIP1beta and MCP-3. Most importantly, in view of the trafficking pattern of these cells, a significant proportion of DC (13% +/- 4% of input cells seeded) was able to migrate across the endothelial basement membrane and, subsequently, across the endothelial barrier (reverse transmigration). The adhesion molecules and chemoattractants characterized herein are likely to underlie the complex trafficking of DC in vivo.

CD11 Antigens↗

Interleukin-6 induces monocyte chemotactic protein-1 in peripheral blood mononuclear cells and in the U937 cell line.

Induction of chemokine gene expression from peripheral blood mononuclear cells (PBMCs) stimulated by proinflammatory cytokines plays an important role in both wound repair and response to infectious agents. In the present study, we show that the proinflammatory cytokine interleukin-6 (IL-6) potently induced mRNA expression and secretion of the CC chemokine monocyte chemotactic protein 1 (MCP-1) in PBMCs. In addition, because human immunodeficiency virus (HIV) infection in vivo and in vitro has been shown to dysregulate the production of and/or the response to cytokines, PBMCs from both healthy uninfected and HIV-infected individuals were studied for their constitutive and IL-6-induced expression of MCP-1. No substantial differences were observed between the two groups of individuals. In addition, IL-6 upregulated MCP-1 expression in the promonocytic cell line U937 and in its chronically HIV-infected counterpart, U1. In these cell lines, IL-6 selectively induced MCP-1 and not other chemokines, including regulated upon activation normal T cells expressed and secreted (RANTES), macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, and IL-8. IL-6 induction of MCP-1 was partially inhibited by hydrocortisone in U1 cells. Thus, IL-6 activates PBMCs to secrete MCP-1, a CC chemokine pivotal for monocyte recruitment in tissue and organs in which important inflammatory events occur.

Anti-Inflammatory Agents↗

IL-10 prevents the differentiation of monocytes to dendritic cells but promotes their maturation to macrophages.

Human monocytes cultured with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-13 for 7 days differentiate into cells with the morphology and function of dendritic cells (DC). We have investigated the effect of IL-10 on this differentiation pathway. In the presence of IL-10 cells did not develop DC morphology, did not express CD1a and had lower levels of MHC class II. IL-10 promoted the differentiation of large cells with the morphology, cytochemistry and membrane phenotype of macrophages, including staining for nonspecific esterase and high levels of CD14, CD16 and CD68. The effect of IL-10 was dose dependent and was best appreciated when the cytokine was added at the initiation of the culture, as addition on day 3 was less inhibitory. When added to already differentiated DC on day 6, IL-10 caused only a modest reduction of MHC class II and CD1a expression, and no acquisition of the macrophage markers CD14, CD16 and CD68. Prolonged incubation up to 5 days with IL-10 did not induce a shift of differentiated DC to macrophages. On the other hand, the macrophages obtained by culturing for 7 days with GM-CSF+IL-13+IL-10 did not shift to DC upon removal of IL-10 for up to 3 days. Thus, the effect of IL-10 on monocyte differentiation, occurs only at the precursor level and confers an irreversible phenotype. From a functional point of view, cells cultured in the presence of IL-10 were poor stimulators of allogeneic cord blood T cells in mixed lymphocyte reaction (MLR) and presented tetanus toxin (TT) to specific T cell lines with much less efficiency than control DC. In contrast, IL-10-cultured DC showed 7 times greater endocytosis of FITC-dextran. This increased endocytosis was mostly mediated via the mannose receptor, as demonstrated by blocking with unlabeled mannose. In conclusion, IL-10 inhibits DC differentiation from monocytes and, in a substantial proportion of the cells, promotes the differentiation to mature macrophages. Intriguingly, IL-10 inhibits antigen presentation while it stimulates endocytic activity.

Antigen Presentation↗

Tumor-driven matrix invasion by infiltrating lymphocytes: involvement of the alpha1 integrin I-domain.

Here we show that tumor cells (TC) from renal cancers regulate the migratory properties of autologous tumor-infiltrating lymphocytes (TIL), enhancing their ability to invade the extracellular matrix. A similar effect is exerted by human recombinant macrophage chemotactic protein 1 (MCP-1) and IL-8, chemokines known to increase T lymphocyte migration both across vascular endothelium and subendothelial matrix. We found that TC freshly derived from renal cell carcinoma surgical specimens constitutively secrete both IL-8 and MCP-1 and that TIL express both specific receptors. TIL matrix invasion elicited by TC is inhibited by the addition of neutralizing antisera specific for IL-8 and MCP-1, demonstrating the direct relationship between chemokine release by TC and TIL invasion. Of note, TIL invasion of the extracellular matrix requires the alpha1 integrin, which acts through its I-domain that is upregulated upon culture with MCP-1 and IL-8. Collectively, these findings suggest that TC may actively recruit TIL via the release of chemotactic factors that enhance an alpha1 integrin-mediated pathway of matrix invasion.

Antigens, CD↗

Isolated premature thelarche and thelarche variant: clinical and auxological follow-up of 119 girls.

Age of thelarche presentation, breast evolution, growth and puberty patterns were retrospectively evaluated in 119 girls with premature thelarche (PT). Thelarche spontaneously presented before 2 yr of chronological age in 80% of girls and completely regressed in 60% of them. Breast regression was significantly more frequent in the patients with more precocious thelarche presentation. In 40% of the girls breast size did not significantly change during a follow-up period ranging from 12 to 134 months (40.6 +/- 32.5). Among the 38 girls who were followed up to an age greater than 8 yr, seven (18.4%) developed central precocious puberty (PP). These 7 patients who progressed into true PP were indistinguishable from girls with normal puberty for age of thelarche presentation, breast size, evolution and auxological features. On the contrary, a subgroup of patients (28.5%) with accelerated height velocity and/or bone age at diagnosis of PT showed an auxological pattern different from normally growing girls during a 3-yr follow-up, but they did not seem to have higher risk of progressing into precocious puberty. In conclusion, PT encompasses different clinical, and perhaps hormonal situations, therefore requiring careful clinical follow-up.

Aging↗

Interleukin-10 increases mannose receptor expression and endocytic activity in monocyte-derived dendritic cells.

Human monocyte-derived dendritic cells were differentiated in vitro for 7 days with granulocyte macrophage-colony stimulating factor and interleukin-13. These cultured dendritic cells are at an immature stage of differentiation and exhert high endocytic activity via surface mannose receptor and via fluid-phase macropinocytosis. We have investigated the modulation of endocytosis by interleukin-10 in these cells. When added during the last 24 h of the 7-day culture, interleukin-10 significantly stimulated the uptake of fluorescein-labelled dextran (39 +/- 16% increase, mean +/- SD of 6 experiments), a sugar binding to the mannose receptor. This effect was dose dependent and correlated with the length of exposure to interleukin-10, with a maximal effect (more than seven-fold increase) when the cytokine was added at the beginning of the culture (day 0). The interleukin-10-increased fluorescein-labelled-dextran endocytosis was mostly mediated via the mannose receptor, as unlabelled mannose and specific antimannose receptor monoclonal antibody inhibited most of the uptake. Moreover, interleukin-10-treated cells expressed increased levels (up to four-fold) of mannose receptor. Interleukin-10 also increased, although to a lesser extent, the fluid-phase endocytosis (macropinocytosis) of fluorescein-labelled albumin. Interleukin-10 had the opposite effect on the differentiation and functional activity of monocyte-derived dendritic cells; cells having a very low stimulatory capacity and reduced expression of MHC class II and CD1a after a 7-day exposure. Thus interleukin-10 had a strong immunosuppressive effect on the differentiation and functional activity of monocyte-derived dendritic cells and yet strongly stimulated endocytosis in these cells. We speculate that an increased endocytic activity would eventually result in a decreased availability of antigens in the external milieu, thus contributing to the immunosuppressive and tolerogenic activity of interleukin-10.

Antibodies, Monoclonal↗

Neurotransmitter-hormonal responses to psychological stress in peripubertal subjects: relationship to aggressive behavior.

The relationship between different degrees of normal aggressiveness (low, medium, high) and neurotransmitter-neuroendocrine responses to the administration of psychologically stressful tests (Mental Arithmetic, Stroop Color Word Interference task, Trial Social Stress test) was examined in thirty male peripubertal junior school adolescents. Plasma concentrations of norepinephrine (NE), epinephrine (EPI), ACTH, cortisol (CORT), growth hormone (GH), prolactin (PRL) and testosterone (T) were measured immediately before the beginning of the tests and at their end, 30 min later. High-normal aggressiveness have been found associated with significantly higher basal concentrations of NE, ACTH, PRL, and T and with a significant increase of GH responses to the stressful stimuli.

Adolescent↗

Rapid retroviral infection of human haemopoietic cells of different lineages: efficient transfer in fresh T cells.

In order to develop a clinically feasible gene marking approach, we have used the recently described PINCO retroviral expression system, composed of the enhanced green fluorescence protein (EGFP) cDNA driven by Moloney MLV LTR and packaged in the Phoenix amphotropic cell line. Two T, five B, one erythromyeloid and three myeloid cell lines were successfully infected with % GFP+ cells ranging from 4% to 79%, showing a lineage-dependent difference in infection susceptibility, with the myeloid cells being the least efficiently infected. We also infected normal mononuclear peripheral cells cultured in PHA and rhIL-2 for 2 d, and obtained an average of 30% GFP+ cells, all present within the CD3+ population, with CD4+ and CD8+ cells being equally infected. Finally, the tonsillar purified B population showed lower levels of infectivity (6%) whereas high susceptibility was shown by normal human umbilical vein endothelial cells (57%). Highly purified CD34+ cells were also susceptible, varying from 6% to 10% GFP+ cells. Immature myeloid/erythroid progenitors have been infected which stably expressed the GFP protein during further differentiation in culture. The GFP+ T cells were FACS-sorted rapidly upon infection, subsequently cultured and the fluorescence intensity monitored. In all cases the difference in percentage of GFP+ cells did not correlate with the percentage of S/G2/M cycling cells as determined at the moment of infection or with the expression levels of Ram-1 amphotrophic receptor. The improved safety of this retroviral system, the rapidity of the technique, the high efficiency of infection with respect to normal T lymphocytes (in this last case higher than previously reported) and the lack of need for in vitro selection make this system favourable for clinical development.

Antigens, CD34↗

Degradation of 2,4,6-trichlorophenol by a specialized organism and by indigenous soil microflora: bioaugmentation and self-remediability for soil restoration.

A selected mixed culture and a strain of Alcaligenes eutrophus TCP were able to totally degrade 2,4,6,-TCP with stoichiometric release of Cl-. In cultures of Alc. eutrophus TCP, a dioxygenated dichlorinated metabolite was detected after 48 h of incubation. Experiments conducted with soil microcosms gave evidence that: the degradative process had a biotic nature and was accompanied by microbial growth; the soil used presented an intrinsic degradative capacity versus 2,4,6-TCP; the specialized organism used as inoculum was effective in degrading 2,4,6-TCP in a short time. These results could be utilized for the adoption of appropriate remediation techniques for contaminated soil.

Alcaligenes↗

Insulin pulsatility in obese and normal prepubertal children.

OBJECTIVE: To assess whether in prepubertal children insulin secretion is pulsatile as in adults and to study the influence of body weight on the pattern of insulin secretion. DESIGN AND PATIENTS: Insulin profiles were obtained by 4-min sampling for 2 h, starting at 08.00 a.m. after an overnight fast in 10 prepubertal obese children (BMI-SDS 4.9 +/- 1.6) and in 6 healthy age-matched controls. Five of the obese children were also studied after weight reduction (Delta BMI-SDS 1.6 +/- 0.4). The data have been analyzed by the Pulsar program. RESULTS: Obese children had higher mean insulin levels, insulin secretory areas under the curve above 0 (AUC0), and AUC above baseline (AUCb), with more frequent peaks of larger amplitude and duration compared to controls. Following weight reduction there was a normalization of AUC0 and mean insulin levels while AUCb, peak frequency, amplitude and duration did not change significantly. Correlation analysis revealed that BMI-SDS was strictly related to the parameters of pulsatile insulin secretion such as AUC0, AUCb, mean insulin level, peak amplitude and peak frequency. CONCLUSIONS: Insulin secretion in children is pulsatile and its secretory pattern is influenced by body weight.

Adult↗

The effect of different growth hormone administration frequencies on growth in growth hormone-deficient patients.

UNLABELLED: In two different groups of clinically prepubertal children (bone age </=8 years) with isolated growth hormone deficit we have evaluated either if the substitutive therapy administered by pump (permitting between 20.00 and 08.00 h the association of continuous and intermittent subcutaneous growth hormone administration) could improve growth (study A) or if a 3 times/week schedule treatment could be performed without any negative effect on growth with respect to 6 injections/week (study B). All patients had been previously successfully treated for at least 2 years by the same dose used during both studies (0.6 IU/kg/week) administered at bedtime 6 times/week. Study A: Each child underwent at bedtime both pump administration (6 months) and single daily injection (6 months). The circulating IGF-I pattern as well as the growth velocity and the ratio bone age increase/height age increase did not differ during the two treatment regimens. Study B: No differences were observed in auxological parameters during the treatment schedule on 3 times/week compared to the previous year on 6 times/week. IN CONCLUSION: Our treatment, consisting of the association of continuous and intermittent subcutaneous growth hormone administration, did not improve growth velocity with respect to single daily subcutaneous injection; the growth hormone administration 3 times/week, starting at the 3rd year of substitutive therapy or later, seems to have no negative effect on growth with respect to 6 injections/week.

Child↗

Interleukin-1beta and interferon-gamma differentially regulate release of monocyte chemotactic protein-1 and interleukin-8 by human bronchial epithelial cells.

Airway inflammation is characterized by an accumulation of activated leukocytes. Bronchial epithelial cells may contribute to this process by releasing chemokines and by expressing surface membrane molecules involved in the adhesion and activation of the recruited leukocytes. In this study, we analyzed the effects of cytokines and glucocorticoids on the release of monocyte chemotactic protein-1 (MCP-1), a potent chemoattractant for predominantly monocytes and lymphocytes, by human bronchial epithelial cells and compared this with the release of interleukin-8 (IL-8), which potently attracts neutrophils. In addition, we analyzed the effects of cytokines and glucocorticoids on the epithelial expression of intercellular adhesion molecule (ICAM)-1, CD40, and human leukocyte antigen (HLA) class II molecules. Primary cultures of human bronchial epithelial cells constitutively released MCP-1 and IL-8. IFN-gamma greatly increased MCP-1 release, which was accompanied by increased expression of MCP-1 mRNA and an increased monocyte chemotactic potential. In contrast, IFN-gamma had no effect on the release of IL-8, but it did increase the epithelial expression of ICAM-1, CD40, and HLA class II molecules. IL-1beta increased both MCP-1 and IL-8 release, and increased the expression of ICAM-1 and CD40, but not HLA class II molecules. Dexamethasone partially inhibited the cytokine-induced release of MCP-1 and IL-8 and the expression of ICAM-1, CD40, and HLA class II molecules by human bronchial epithelial cells. Our results indicate that IFN-gamma and IL-1beta differentially regulate the MCP-1 and IL-8 release by human bronchial epithelial cells. In addition, IL-1beta and particularly IFN-gamma increase the expression of ICAM-1, HLA class II and/or CD40 molecules, which are involved in the adhesion and possibly activation of the recruited leukocytes. Finally, the beneficial effect of glucocorticoid therapy in airway inflammatory diseases may be mediated in part by inhibition of chemokine release and ICAM-1, CD40, and HLA class II expression by bronchial epithelial cells.

Bronchi↗