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Biomedical subjects

A Antonelli

Publications and source records attributed to A Antonelli.

At least 163 records · Page 9Linked to original sources

Cytogenetic investigations on Werner's syndrome, Acrogeria and Keratosis Palmo-Plantaris.

The frequencies of sister chromatid exchanges and of aspecific chromosome aberrations have been investigated in the lymphocytes from a Werner patient, from an Acrogeria patient and from three members of a family with Keratosis Palmo-Plantaris. These investigations point out that: 1) the SCE frequency is significatively enhanced in Werner as in KPP lymphocytes, 2) the frequency of aspecific chromosome aberrations is increased only in Werner lymphocytes, without evidence of variegated translocation mosaicism. The findings confirm that SCE and chromosome aberrations do not necessarily result from the same genetic damage and that SCE may represent the cytological evidence of unexcised non fatal DNA lesions, which occasionally may be responsible for carcinogenesis.

Chromosome Aberrations↗

[Water-electrolyte and acid-base changes during extracorporeal circulation].

Changes in fluid, electrolyte and acid-base balance were evaluated in 8 patients during extracorporeal circulation. H2O increase and osmolarity and colloid osmotic pressure decrease, due to priming and perfusion technique used for cardiopulmonary by pass, were found. Mild respiratory alkalosis was also present. K+ serum, because of KCL supplements, was always maintained within the normal values, while Na+ serum concentration was low, despite of large amounts of Na+ infused during perfusion. After examination of disturbances in fluid, electrolyte and acid-base balance, the Authors report the performed corrections and emphasize the importance of a prompt recognition and the immediate therapy of these changes to avert serious cardiac impairments during extracorporeal circulation or during the immediate postoperative period.

Acid-Base Equilibrium↗

Some effects of the stimulus repetition rate on N1 and N2 in transtympanic and surface recordings.

The early auditory evoked electrical activity has been recorded in man at the promontory (transtympanic approach) and on the scalp vertex-mastoid derivation), in response to clicks delivered at different rates. Latency and amplitude of the first two peaks (N1 and N2), as a function of the repetition rate, have been measured and compared. The differences between the latencies of transtympanic and surface N1 are very small, at any rate, with a maximum value of 0.08 msec. In the transtympanic recording, the latency difference between N2 and N1 is constant throughout the whole range of rate values, from 3 to 100 clicks per second. In the surface responses, on the contrary, the latency difference between N2 and N1 tends to increase as the rate is increased. The amplitude of the transtympanic N2 is consistently reduced at click rates above 20-50 per second (more markedly than the amplitude of N1), while the amplitude of the surface N2 is much more insensitive to the rate increase. Some implications of these results are discussed with respect to the origin of N2 in the two recording conditions.

Action Potentials↗

Peculiar mosaicism 47,XYY/48,XYYY/49,XYYYY in man.

The chromosome analysis in a 9 years-old boy showed the presence of three cell lines : 47,XYY (28%) ; 48,XYYY (68%); 49,XYYYY (4%). Since the most frequent cells bear three Y chromosomes and the karyotype of the propositu's father is normal, it is suggest that the propositus arose from an YYY sperm and that the observed mosaicism originated from a subsequent postzygotic non-disjunction.

Child↗

Modulation of ICAM-1 expression in ECV304 cells by macrophage-released cytokines.

Transendothelial leukocyte trafficking during inflammation requires the expression of adhesion molecules such as human intercellular adhesion molecule-1 (ICAM-1). ICAM-1 is constitutively expressed on the surface of endothelial cells and its levels increase in response to a variety of inflammatory mediators, including cytokines. Monocyte/macrophage cells play a crucial role in this context because, upon stimulation, they release proinflammatory cytokines which are responsible for the upregulation of adhesion molecules in endothelial cells. In the present study we investigated whether the modulation of macrophage activation and cytokine release is able to modulate ICAM-1 expression in endothelial cells. Dexamethasone was selectively delivered to macrophages by means of a red blood cell-mediated delivery system. Subsequent stimulation of macrophages by lipopolysaccharide (LPS) was found to inhibit NF-kB activation and tumor necrosis factor-alpha (TNF-alpha) release [R. Crinelli, A. Antonelli, M. Bianchi, L. Gentilini, S. Scaramucci, and M. Magnani (2000) Blood Cells Mol. Dis. 26, 211-222]. Incubation with conditioned medium derived from LPS-stimulated macrophages receiving dexamethasone resulted in a 45% inhibition of ICAM-1 mRNA expression in ECV304 cells. In the same experimental system this reduced ICAM-1 expression was paralleled by a reduced NF-kB DNA binding activity and a twofold higher level of IkB(alpha) in the cytosol of endothelial cells. Activation of ICAM-1 expression in ECV304 cells by macrophage-conditioned medium is not due to IFN-gamma stimulation since STAT-1 DNA binding remained unchanged. Furthermore, treatment of the macrophage-conditioned medium with a TNF-alpha-inactivating antibody resulted in the complete abrogation of induced ICAM-1 expression. These results suggest that TNF-alpha is the main cytokine released by LPS-stimulated macrophages able to promote ICAM-1 gene expression in endothelial cells. Modulation of the NF-kB activation pathway in macrophages by targeted delivery of dexamethasone could potentially be used as a therapeutic strategy with which to inhibit the expression of ICAM-1 in endothelial cells.

Anti-Inflammatory Agents↗

CD38 autoimmunity: recent advances and relevance to human diabetes.

Human CD38 is a protein which catalyzes the synthesis of nicotinic acid adenine dinucleotide (NAADP+) and the conversion of NAD+ to cADPR. Both cADPR and NAADP+ are powerful intracellular Ca2+ ([Ca2+]i) mobilizers in different cell types. Recently, the presence of CD38 autoantibodies has been found in a significant number (9-15%) of patients with Type 2 or long-standing Type 1 diabetes. These autoantibodies are biologically active, the majority of them (-60%) displaying agonistic properties, i.e., [Ca2+]i mobilization in lymphocytic cell lines and in pancreatic islets. In cultured rat pancreatic islets, the human autoantibodies inhibit glucose-induced insulin release, whereas, in human pancreatic islets CD38 autoantibodies stimulate glucose-mediated insulin secretion. The clinical phenotype of anti-CD38-positive Type 2 diabetes differs from the LADA (latent autoimmune diabetes of adults) phenotype. When accurately matched for age and obesity, only LADA patients with anti-GAD antibodies, but not GAD-negative/ CD38-positive patients, have reduced in vivo beta-cell function in comparison to antibody-negative patients. Transgenic mice overexpressing CD38 show enhanced glucose-induced insulin release, whereas, conversely, CD38 knockout mice display a severe impairment in beta-cell function. Few Japanese diabetic patients carry a missense mutation in the CD38 gene; in Caucasian patients mutations in the CD38 gene have not been found. Collectively, these findings suggest that activation of CD38 represents an alternative signaling pathway for glucose-induced insulin secretion in human beta-cells. More information, however, is necessary to gauge the role of CD38 autoimmunity in the context of the natural history of human Type 1 or Type 2 diabetes.

ADP-ribosyl Cyclase↗

Human lung fibroblast response to NGF, IL-1beta, and dexamethsone.

It has been shown that lung mast cells, eosinophils, and fibroblasts are receptive to the action of nerve growth factor (NGF) and that NGF is released in to the bloodstream of subjects affected by allergic inflammatory response. The role of NGF in lung inflammatory disorders is unclear because there is evidence suggesting that NGF can be involved in both proinflammatory and anti-inflammatory responses. Lung fibroblasts play a marked role in inflammation. In this study we investigated the effect of NGF, interleukin 1beta (II-1beta), and dexamethasone (DEX) on human lung fibroblasts in vitro. We found that II-1beta, but not NGF, promotes fibroblasts' survival and that NGF stimulates trkA receptor expression, down regulates TFG-alpha, and has no effect on TNF-beta immunoreactivity. Moreover, DEX exerts different effects on NGF release by fibroblasts pre-exposed to II-1gamma. Our findings suggest that the NGF released by lung fibroblast during inflammation is not associated with the increase of proinflammatory factors such as TNF-alpha and II-1beta.

Animals↗

The pR plasmid: a tool for discriminating between DNA lesions induced by different types of cytotoxic agents in cultured mammalian cells.

The LA-D cells, obtained by cotransformation of LTA mouse cells (tk- aprt-) with pR plasmid and with tk gene as selective marker, are significantly more resistant to UV light and 4-nitroquinoline-N-1-oxide than LTA control cells. In this work, we report that the LA-D cells exhibit different degrees of response to various DNA-damaging agents: wild-type survival to mitomycin, increased sensitivity to bleomycin, cis-diamminedichloroplatinum and N-methyl-N'-nitro-N-nitrosoguanidine. The pR plasmid could, therefore, play an important role in the DNA-repair mechanisms that modulate the cytotoxic effect of the DNA-inhibitory agents. The possible interactions between pR plasmid products and the different repair enzymes involved are discussed.

Animals↗

Is occupationally induced exposure to radiation a risk factor of thyroid nodule formation?

The prevalence of thyroid nodules was studied with ultrasonography in a group of male hospital workers (n = 44) who had been exposed occupationally to x-rays. This group was compared with a group of nonexposed workers (n = 88) who were age- and sex-matched with the exposed workers. Thyroid nodules were detected in 18 (41%) of the exposed workers, compared with 11 (13%) of the nonexposed controls. Both groups were subdivided with respect to age (i.e., 30-39 y, 40-49 y, 50-59 y), and there was a higher and significant relative risk for thyroid nodule formation in the exposed group. We also divided the groups into subgroups according to levels of exposure (i.e., nonexposed, exposed for < 20 y, and exposed for > 20 y), and a significant result was obtained with the linear-trend chi-square test. The preliminary results of our study suggest that occupationally induced exposure to radiation may be a risk factor for thyroid nodule formation.

Adult↗

Altered plasma nerve growth factor-like immunoreactivity and nerve growth factor-receptor expression in human old age.

BACKGROUND: Nerve growth factor (NGF), discovered because of its action on cells in the peripheral and the central nervous system, is now known to act also on immune cells in developing and adult subjects. Whether peripheral lymphocytes of aged subjects are responsive to this molecule is less clear. OBJECTIVE: Aim of our study was to investigate whether or not plasma NGF undergoes any significant changes during aging and whether or not NGF receptors on peripheral lymphocytes are affected in old subjects. METHODS: To address these questions, we used RT-PCR, immunohistochemistry, and immunoenzymatic analysis to evaluate the expression of NGF receptors in human peripheral lymphocytes and NGF-like immunoreactivity. RESULTS: These results revealed a low amount of NGF in the plasma of old subjects associated with a reduced expression of mRNA for NGF receptor trkA in peripheral lymphocytes. They also showed elevated levels of circulating interleukin-1beta (IL-1beta), and interleukin-6 (IL-6) in the bloodstream of adult and aged subjects. CONCLUSION: Our data indicate that peripheral lymphocytes are targets for circulating NGF and suggest that changes in NGF-receptor expression on lymphocytes might be potential marker for aging lymphocytes.

Adult↗