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Biomedical subjects

B Marchetti

Publications and source records attributed to B Marchetti.

At least 19 recordsLinked to original sources
PubMed2006

The E5 oncoprotein of BPV-4 does not interfere with the biosynthetic pathway of non-classical MHC class I.

The major histocompatibility complex (MHC) class I region in mammals contains both classical and non-classical MHC class I genes. Classical MHC class I molecules present antigenic peptides to cytotoxic T lymphocytes, whereas non-classical MHC class I molecules have a variety of functions. Both classical and non-classical MHC molecules interact with natural killer cell receptors and may under some circumstances prevent cell death by natural killer cytotoxicity. The E5 oncoprotein of BPV-4 down-regulates the expression of classical MHC class I on the cell surface and retains the complex in the Golgi apparatus. The inhibition of classical MHC class I to the cell surface results from both the impaired acidification of the Golgi, due to the interaction of E5 with subunit c of the H+ V-ATPase, and to the physical binding of E5 to the heavy chain of MHC class I. Despite the profound effect of E5 on classical MHC class I, E5 does not retain a non-classical MHC class I in the Golgi, does not inhibit its transport to the cell surface and does not bind its heavy chain. We conclude that, as is the case for HPV-16 E5, BPV-4 E5 does not down-regulate certain non-classical MHC class I, potentially providing a mechanism for the escape of the infected cell from attack by both cytotoxic T lymphocytes and NK cells.

Animals↗
PubMed2006

The E5 protein of BPV-4 interacts with the heavy chain of MHC class I and irreversibly retains the MHC complex in the Golgi apparatus.

BPV-4 E5 inhibits transcription of the bovine MHC class I heavy chain (HC) gene, increases degradation of HC and downregulates surface expression of MHC class I by retaining the complex in the Golgi apparatus (GA). Here we report that transcription inhibition can be alleviated by interferon treatment and the degradation of HC can be reversed by treatment with inhibitors of proteasomes and lysosomes. However, the inhibition of transport of MHC class I to the cell surface is irreversible. We show that E5 is capable of physically interacting with HC. Together with the inhibition of the vacuolar ATPase (due to the interaction between E5 and 16k subunit c), the interaction between E5 and HC is likely to be responsible for retention of MHC class I in the GA. C-terminus deletion mutants of E5 are incapable of either downregulating surface MHC class I or interacting with HC, establishing that the C-terminus domain of E5 is important in the inhibition of MHC class I.

Animals↗
PubMed2006

Inflammatory biomarkers in blood of patients with acute brain ischemia.

Although many failed surrogate markers are provided in the literature, inflammation may contribute to the outcome of ischemic stroke. In 50 consecutive patients with acute ischemic stroke, in the absence of symptoms and signs of concomitant infection, we evaluated a panel of biomarkers reported to be variably associated with brain ischemia, and correlate their serum level with the brain lesion volume and clinical outcome. Infarct size was calculated on computed tomography (CT) scans by means of the Cavalieri's method. Neurological impairment was scored by using the Glasgow Coma Scale, Glasgow Outcome Scale and National Institutes of Health (NIH) scales at stroke onset and 3-month follow-up. Some markers showed a direct significant correlation with both initial and final NIH scale and with infarct size, particularly tumor necrosis factor alpha (TNF-alpha) (P=0.002), intercellular adhesion molecule-1 (P<0.01) and matrix metalloproteinase-2/9 (P=0.001). In contrast to previous reports, interleukin-6 (IL-6) serum level showed a significant inverse correlation with both final neurological impairment and infarct size (P<0.001). This novel finding allows us suggesting that IL-6, in the context of a complex pro-inflammatory network occurring during stroke, is associated with neuroprotection rather than neurotoxicity in patients with ischemic brain injury.

Acute Disease↗
PubMed2005

Estrogen, neuroinflammation and neuroprotection in Parkinson's disease: glia dictates resistance versus vulnerability to neurodegeneration.

Post-menopausal estrogen deficiency is recognized to play a pivotal role in the pathogenesis of a number of age-related diseases in women, such as osteoporosis, coronary heart disease and Alzheimer's disease. There are also sexual differences in the progression of diseases associated with the nigrostriatal dopaminergic system, such as Parkinson's disease, a chronic progressive degenerative disorder characterized by the selective degeneration of mesencephalic dopaminergic neurons in the substancia nigra pars compacta. The mechanism(s) responsible for dopaminergic neuron degeneration in Parkinson's disease are still unknown, but oxidative stress and neuroinflammation are believed to play a key role in nigrostriatal dopaminergic neuron demise. Estrogen neuroprotective effects have been widely reported in a number of neuronal cell systems including the nigrostriatal dopaminergic neurons, via both genomic and non-genomic effects, however, little is known on estrogen modulation of astrocyte and microglia function in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease. We here highlight estrogen modulation of glial neuroinflammatory reaction in the protection of mesencephalic dopaminergic neurons and emphasize the cardinal role of glia-neuron crosstalk in directing neuroprotection vs neurodegeneration. In particular, the specific role of astroglia and its pro-/anti-inflammatory mechanisms in estrogen neuroprotection are presented. This study shows that astrocyte and microglia response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine injury vary according to the estrogenic status with direct consequences for dopaminergic neuron survival, recovery and repair. These findings provide a new insight into the protective action of estrogen that may possibly contribute to the development of novel therapeutic treatment strategies for Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2004

Downregulation of major histocompatibility complex class I in bovine papillomas.

Bovine papillomavirus (BPV) induces papillomas in cattle; in the great majority of cases, these regress due to the host immune response, but they can persist and progress to malignancy. Even in the absence of malignant transformation, BPV infection persists for a significant period of time before activation of the host immune system, suggesting that the host immune system is unaware of, or disabled by, BPV. E5 is the major oncoprotein of BPV, which, in addition to its transforming properties, downregulates the expression and transport to the cell surface of major histocompatibility complex class I (MHC I). Here, it is shown that co-expression of MHC I and E5 in papillomas caused by BPV-4 infection is mutually exclusive, in agreement with the inhibition of surface MHC I expression by E5 that is observed in vitro. The inhibition of MHC expression in E5-expressing papilloma cells could explain the long period that is required for activation of the immune response and has implications for the progression of papillomas to the malignant stage; absence of peptide presentation by MHC I to cytotoxic T lymphocytes would allow the infected cells to evade the host cellular immune response and allow the lesions to persist.

Animals↗
PubMed2003

The reproductive system at the neuroendocrine-immune interface: focus on LHRH, estrogens and growth factors in LHRH neuron-glial interactions.

Bidirectional communication between the neuroendocrine and immune systems plays a pivotal role in health and disease. Signals generated by the hypothalamic-pituitary-gonadal (HPG) axis (i.e. luteinizing hormone-releasing hormone, LHRH, and sex steroids) are major players coordinating the development immune system function. Conversely, products generated by immune system activation exert powerful and longlasting effects on HPG axis activity. In the central nervous system (CNS), one chief neuroendocrine-immune (NEI) compartment is represented by the astroglial cell population and its mediators. Of special interest, the major supporting cells of the brain and the thymus, astrocytes and thymic epithelial cells, share a similar origin and a similar set of peptides, transmitters, hormones and cytokines functioning as paracrine/autocrine regulators. This may explain some fundamental analogies in LHRH regulation of both cell types during ontogeny and in adult life. Hence, the neuropeptide LHRH significantly modulates astrocyte and thymic cell development and function. Here we focus this work on LHRH neuron-glial signaling cascades which dictate major changes during LHRH neuronal differentiation and growth as well as in response to hormonal manipulations and pro-inflammatory challenges. The interplay between LHRH, growth factors, estrogens and pro-inflammatory mediators will be discussed, and the potential physiopathological implications of these findings summarized. The overall study highlights the plasticity of this intersystem cross-talk and emphasize neuron-glial interactions as a key regulatory level of neuroendocrine axes activity.

Animals↗
PubMed2001

Effect of 17-beta estradiol and epidermal growth factor on DNA and RNA labeling in astroglial cells during development, maturation and differentiation in culture.

Growth factors stimulate astroglial and neuronal proliferation and differentiation in culture. Estrogens markedly influence astroglia, and are key factors participating in neurodegeneration. The aim of the present study was to investigate interactions between estradiol (E2) and epidermal growth factor (EGF) during astroglia development, maturation and differentiation in culture. DNA or RNA labeling in 16 or 40 or 60 days in vitro (DIV) astrocyte cultures treated for 24 or 48 h with EGF and/or E2 was evaluated. A significant increase in DNA labeling in 16 DIV astrocyte cultures treated for 24 h with EGF (5 ng/ml) and E2 (1 nM) was found. EGF (5 or 10 ng/ml) addition in the last 24 h in 48 h E2 (1 or 5 nM)-treated astrocyte cultures at 16 DIV caused a slight, but significant increase in DNA labeling. No differences in RNA labeling were observed in 16 DIV astrocyte cultures treated for 24 or 48 h with EGF (5 or 10 ng/ml) in the presence of E(2) (1 or 5 nM). A significant stimulation in DNA labeling was shown in 40 DIV astrocyte cultures treated for 48 h with E2 (1 or 5 nM) in the presence of EGF (5 or 10 ng/ml) added in the last 24 h. In well differentiated astroglial cell cultures (60 DIV), DNA labeling was remarkably increased after 24 h treatment with 1 nM E2 or 5 ng/ml EGF. Co-addition of 1 nM E2 and 5 ng/ml EGF for 24 h reduced [methyl-(3)H]thymidine incorporation, when data are compared to E2- or EGF-treated cultures. Addition of EGF in the presence of E2 for 48 h or only in the last 24 h caused a significant decrease of [methyl-(3)H]thymidine incorporation in comparison with EGF-treated cultures at 60 DIV or with untreated cultures. Treatment of cultures for 24 h with EGF (5 or 10 ng/ml) alone or in combination with E2 (1 or 5 nM) induced a strong increase of RNA labeling in 60 DIV astrocyte cultures. Addition for 48 h of E2 (1 or 5 nM) or EGF (5 or 10 ng/ml) alone or in association stimulated significantly RNA labeling in astrocyte cultures at 60 DIV. When 60 DIV astrocyte cultures were treated for 48 h with E2 (1 or 5 nM) in the presence of EGF (5 or 10 ng/ml) added only in the last 24 h, a potentiating effect of RNA labeling was observed. The above results suggest that interaction between growth factors and estrogens may contribute to regulate astroglia development, maturation and differentiation.

Astrocytes↗
PubMed2001

Stress, glucocorticoids and the susceptibility to develop autoimmune disorders of the central nervous system.

Alterations of the immunoendocrine circuit along the hypothalamic-pituitary-adrenocortical (HPA) axis in various autoimmune diseases have recently been observed, suggesting a modulatory role of this feedback regulation in the pathogenesis of autoimmune diseases. Susceptibility to experimental autoimmune encephalomyelitis (EAE) may be influenced by variations in the production of endogenous glucocorticoid hormones (GC). The adrenocortical response is central to recovery from EAE in the Lewis rat, as reflected by increased severity of the disease in adrenalectomized animals. The key role of GC in modifying the induction and progression of EAE is also emphasized by a reversal of corticoid-mediated effects through treatment with glucocorticoid receptor (GR) antagonists. We studied the relationship between defective GR function and susceptibility to EAE in transgenic (Tg) mice expressing GR antisense RNA. EAE was induced with the encephalitogenic myelin oligodendrocyte peptide (pMOG 36-50) in wild type (Wt) and transgenic (Tg) female mice bearing GR antisense RNA. pMOG 36-50 induced typical EAE in Wt mice but not in Tg mice. Histological examination of brains and spinal cords of Wt mice showed the presence of inflammation and/or demyelination, whereas in Tg mice neither were present. Although the mechanisms underlying the resistance of Tg mice to EAE induction are not yet clarified, compensatory changes at different levels of the HPA-immune axis in response to the potent immunogenic challenge are likely to participate in the observed effects. This work underlies the plasticity of the HPA-immune axis and suggests that pharmacological manipulation of neuroendocrine-immune networks may be a therapy of multiple sclerosis.

Animals↗
PubMed2001

Stress, the immune system and vulnerability to degenerative disorders of the central nervous system in transgenic mice expressing glucocorticoid receptor antisense RNA.

Current research evidence suggests that interactions between genetic and environmental factors contribute to modulate the susceptibility to degenerative disorders, including inflammatory and autoimmune diseases of the central nervous system (CNS). In this context, bidirectional communication between the neuroendocrine and immune systems during ontogeny plays a pivotal role in programming the development of neuroendocrine and immune responses in adult life, thereby influencing the predisposition to several disease entities. Glucocorticoids (GCs), the end products of the hypothalamic-pituitary-adrenocortical (HPA) axis, gender and signals generated by hypothalamic-pituitary-gonadal (HPG) axis are major players coordinating the development of immune system function and exerting powerful effects in the susceptibility to autoimmune disorders, including experimental autoimmune encephalomyelitis (EAE), the experimental model for multiple sclerosis (MS). In particular, GCs exert their beneficial immunosuppressive and anti-inflammatory effects in inflammatory disorders of the CNS, after binding to their cytoplasmic receptors (GRs). Here we review our work using transgenic (Tg) mice with a dysfunctional GR from early embryonic life on programming vulnerability to EAE. The GR-deficiency of these Tg mice confers resistance to active EAE induction. The interplay between GCs, proinflammatory mediators, gender and EAE is summarized. On the basis of our data, it does appear that exposure to a defective GR through development programs major changes in endogenous neuroendocrine and immune mechanisms controlling the vulnerability to EAE. These studies highlight the plasticity of the HPA-immune axis and its pharmacological manipulation in autoimmune diseases of the CNS.

Animals↗
PubMed2001

[Evaluation of 7 endoscope washer-disinfectors: bactericidal activity of the disinfectants, antibacterial efficacity of paired washer-disinfector products].

The authors studied seven automatic washer disinfectors for flexible endoscopes with two methods. The first method, a microdilution method, studied the bactericidal activity of the seven disinfectants against 21 strains: four reference strains, 14 hospital strains reported in the literature as nosocomial strains responsible for infections transmitted by flexible endoscopes and three vancomycin-resistant Enterococci. The ability of the seven automatic washer disinfectors to decontaminate flexible endoscopes following inoculation with four reference strains was studied with the second method. There were three kinds of results: the results of three automatic washer disinfectors in conformity with both methods; the results of three automatic washer disinfectors conformity with 1 method only; the results of one automatic washer disinfector without conformity with any methods. Both methods should be used for evaluation of automatic washer disinfector. Then, these results emphasize the necessity to modify the use of disinfectants and/or the systems of some automatic washer disinfectors.

Anti-Bacterial Agents↗
PubMed2001

Neuroendocrine-immune (NEI) circuitry from neuron-glial interactions to function: Focus on gender and HPA-HPG interactions on early programming of the NEI system.

Bidirectional communication between the neuroendocrine and immune systems during ontogeny plays a pivotal role in programming the development of neuroendocrine and immune responses in adult life. Signals generated by the hypothalamic-pituitary-gonadal axis (i.e. luteinizing hormone-releasing hormone, LHRH, and sex steroids), and by the hypothalamic-pituitary-adrenocortical axis (glucocorticoids (GC)), are major players coordinating the development of immune system function. Conversely, products generated by immune system activation exert a powerful and long-lasting regulation on neuroendocrine axes activity. The neuroendocrine-immune system is very sensitive to preperinatal experiences, including hormonal manipulations and immune challenges, which may influence the future predisposition to several disease entities. We review our work on the ongoing mutual regulation of neuroendocrine and immune cell activities, both at a cellular and molecular level. In the central nervous system, one chief compartment is represented by the astroglial cell and its mediators. Hence, neuron-glial signalling cascades dictate major changes in response to hormonal manipulations and pro-inflammatory triggers. The interplay between LHRH, sex steroids, GC and pro-inflammatory mediators in some physiological and pathological states, together with the potential clinical implications of these findings, are summarized. The overall study highlights the plasticity of this intersystem cross-talk for pharmacological targeting with drugs acting at the neuroendocrine-immune interface.

Animals↗
PubMed2001

Evaluation of the microbicidal efficacy of Steris System I for digestive endoscopes using GERMANDE and ASTM validation protocols.

In the light of more and more invasive procedures being carried out in digestive endoscopy using sterile devices, it appears necessary to put in place a process of endoscope reprocessing capable of ensuring the complete elimination of micro-organisms contaminating the device. We undertook a study of the microbial efficacy of STERIS SYSTEM 1 (SS1) which purports to achieve this objective. The channels of a gastroscope and a colonoscope were contaminated with suspensions of Pseudomonas aeruginosa, Aspergillus niger and Bacillus subtilis spores. Two procedures were then followed: (1) manual washing only, and (2) treatment in SS1 without prewashing. Recoveries of organisms were made from each channel according to a standard methodology to discover any survivors. Contamination controls we re assessed to measure the logarithmic reduction between the initial contamination and that recovered from the channels. Six cycles per micro-organisms, per type of endoscope, and per type of procedure were carried out. From an initial contamination leve l of 10(6) micro-organisms per endoscope, no micro-organisms were recovered in 35 of the 36 cycles with the SS1. In one cycle with the colonoscope, three B. subtilis organisms were recovered from the channels. Washing only gave microbial reductions which varied according to the micro-organism tested. The maximum reduction with washing alone was by a factor of 10(3 +/- 0.1)for B. subtilis and the minimum reduction factor was 10(3 +/- 0.3)for P. aeruginosa. Considering the results obtained with SS1 without prewashing and the efficacy obtained from washing only, the washing step offers an additional antimicrobial assurance reduction factor of between 10 and 103.1. This study shows that SS1, integrated into an overall reprocessing procedure for digestive endoscopes, is capable of delivering the complete elimination of contaminating micro-organisms in a reduced time and eliminates the toxic risk of reprocessing associated with aldehyde based disinfectants.

Disinfectants↗
PubMed2000

Basic fibroblast growth factor (bFGF) acts on both neurons and glia to mediate the neurotrophic effects of astrocytes on LHRH neurons in culture.

Luteinizing hormone-releasing hormone (LHRH) neurons play a pivotal role in the neuroendocrine control of mammalian reproduction. Astrocytes were shown to be involved in the regulation of LHRH neuronal function, but little is known about the contribution of astroglial-derived factors in the regulation of LHRH neuron development. In order to gain insight into the mechanisms regulating the development of these cells, at morphological and biochemical levels we characterized the neurotrophic effects exerted by young astrocytes (maintained in culture for 8 days in vitro) and old astrocytes (maintained 26 days) on the differentiation, proliferation, and phenotypic expression of immortalized hypothalamic LHRH (GT(1-1)) neurons in vitro. Culturing GT(1-1) cells in the presence of young glia for different time intervals caused a marked acceleration in the acquisition of their neuronal phenotype. At all times examined, GT(1-1) cells cocultured with young glia exhibited a significantly greater extension of processes/cell, larger number of processes/cell and greater surface area of growth cones than GT(1-1) cells grown over nonglial adhesive substrates (polylysine). By contrast, when GT(1-1) neurons were cocultured with old glia, the length of neuronal processes and the growth cone surface area were significantly lower than in control GT(1-1) neurons cultured in the absence of glia. At 3 days in vitro (DIV), GT(1-1) neurons cocultured with young glia exhibited a 50% lower incorporation of [(3)H]thymidine than GT(1-1) neurons cultured without glia. By contrast, in the presence of old glia [(3)H]thymidine incorporation was significantly higher in cells cocultured with glia than in GT(1-1) neurons cultured alone. Localization of the proliferating cells by dual immunohistochemical staining revealed that the incorporation of bromodeoxiuridine (BrdU) was restricted to nuclei of GT(1-1) neurons when these were cocultured with young glia, but associated with both neurons and astrocytes in the presence of old glia. At the functional level, coculture of GT(1-1) neurons with young glia increased the spontaneous release of LHRH as compared to GT(1-1) neurons grown in the absence of glia. By contrast, in the presence of old glia LHRH release in the medium was significantly lower than in controls. Conditioned medium of young glia (ACM-Y) induced significant neurotrophic and functional effects on GT(1-1) cells, but these effects were 50% less potent than the coculture itself. Heat denaturation of ACM-Y totally abolished its neurotrophic and functional properties, indicating that they involved a peptide factor. Suppression of bFGF activity in ACM-Y reduced its neurotrophic activity by approximately 40%, but did not affect its LHRH release-promoting effects. By contrast, neutralization of endogenous bFGF activity in GT(1-1) neurons cocultured with young glia counteracted both neurotrophic and functional effects of young glia. Treatment of old glia with bFGF rescued its neurotrophic and functional effects on GT(1-1) cells. Moreover, the ACM of aged bFGF-treated old glia was the most powerful neurotrophic stimulus for GT(1-1) neurons. These results suggest that: 1) soluble peptidic factors, including bFGF, and mechanism(s) requiring coculture are responsible for the highly potent neurotrophic and functional effects of young glia; 2) the inhibitory effects of old glia on neurite outgrowth and LHRH release are mediated in part by soluble inhibitory molecules and in part by factors requiring coculture with old glia; 3) old glia may revert to a growth-supporting state when treated with bFGF and this functional shift involves a diffusible molecule with potent neurotrophic and functional effects on immortalized LHRH neurons. (c) 2000 Wiley-Liss, Inc.

Animals↗