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Biomedical subjects

O Rossi

Publications and source records attributed to O Rossi.

At least 19 recordsLinked to original sources
PubMed2006

Sublingual immunotherapy with Dermatophagoides monomeric allergoid down-regulates allergen-specific immunoglobulin E and increases both interferon-gamma- and interleukin-10-production.

BACKGROUND: The clinical efficacy and safety of sublingual immunotherapy (SLIT) for aeroallergens has been demonstrated in several trials, whereas the immunological changes induced by this treatment, which may account for the clinical improvement, are still unclear. OBJECTIVE: To investigate the effects of a successful SLIT on the in vitro allergen-driven T cell response and cytokine secretion as well as on the serum levels of chemokines and of IgE, IgG1 and IgG4 antibodies (Abs). MATERIALS AND METHODS: Twenty-five Dermatophagoides pteronyssinus (Dp)-sensitive patients with perennial rhinitic and/or rhinitic and asthmatic symptoms were randomized into two groups (13 untreated (UT) and 12 SLIT-treated) for a 1 year and half study. The proliferative response of peripheral blood mononuclear cell (PBMC) to purified Der p1 allergen, their cytokines (IFN-gamma, IL-4, IL-10 and TGF-beta) production and serum levels of chemokines associated with T helper type 1 (Th1) (CXCL10) or T helper type 2 (Th2) (CCL22) responses and of Dp-specific IgE, IgG1 and IgG4 Abs were evaluated before and after 6 months of treatment. RESULTS: SLIT induced a significant reduction of symptom medication scores after 6, 12 and 18 months of treatment in comparison with UT patients. SLIT-treated patients showed a significant decrease in serum levels of DP-specific IgE Abs, whereas total IgE, and specific IgG1 and IgG4 Abs remained unchanged. The proliferative response of allergen-specific T cells to Der p1 in vitro after 6 months of treatment was reduced, while no effect was observed on T cell proliferation to recall antigen (streptokinase). Moreover, Der p1-driven IFN-gamma and IL-10 were significantly increased in culture supernatants of PBMC from 6 month-treated patients in comparison with those detected at the beginning of therapy. CONCLUSIONS: These data suggest that the allergen-driven enhancement of IL-10- and IFN-gamma-producing T cells precedes and associates with SLIT-induced down-regulation of specific IgE, thus providing a rationale to explain the clinical benefit of SLIT in allergic patients.

Administration, Sublingual↗
PubMed2001

The purine degradation pathway: possible role in paralytic shellfish toxin metabolism in the cyanobacterium Planktothrix sp. FP1.

The paralytic shellfish toxins (PSTs) are potent neurotoxic alkaloids and their major biological effect is due to the blockage of voltage-gated sodium channels in excitable cells. They have been recognised as an important health risk for humans, animals, and ecosystems worldwide. The metabolic pathways that lead to the production and the degradation of these toxic metabolites are still unknown. In this study, we investigated the possible link between PST accumulation and the activation of the metabolism that leads to purine degradation in the filamentous freshwater cyanobacterium Planktothrix sp. FP1. The purine catabolic pathway is related to the nitrogen microcycle in water environments, in which cyanobacteria use traces of purines and ureides as a nitrogen source for growth. Thus, the activity of allantoicase, a key inducible enzyme of this metabolism, was used as tool for assaying the activation of the purine degradation pathway. The enzyme and the pathway were induced by allantoic acid, the direct substrate of allantoicase, as well as by adenine and, to a lower degree, by urea, one of the main products of purine catabolism. Crude cell extract of Escherichia coli was also employed and showed the best induction of allantoicase activity. In culture, Planktothrix sp. FP1 showed a differential accumulation of PST in consequence of the induction with different substrates. The cyanobacterial culture induced with allantoic acid accumulated 61.7% more toxins in comparison with the control. On the other hand, the cultures induced with adenine, urea, and the E. coli extract showed low PST accumulation, respectively, 1%, 38%, and 5% of the total toxins content detected in the noninduced culture. A degradation pathway for the PSTs can be hypothesised: as suggested for purine alkaloids in higher plants, saxitoxin (STX) and derivatives may also be converted into xanthine, urea, and further to CO2 and NH4+ or recycled in the primary metabolism through the purine degradation pathway.

Cyanobacteria↗
PubMed2000

Analysis of repair of abasic sites in early onset breast cancer patients.

Defective DNA repair has been suggested as a possible predisposing factor for breast cancer. We have investigated the repair of the frequent endogenous lesions abasic sites in sporadic early onset breast cancer patients and matched control individuals. No significant difference was observed between the abasic site repair capacities of peripheral blood lymphocytes from cases and controls. Repair of abasic sites was also studied in tumor and surrounding normal tissues of the patients. The 2 tissues showed marked differences in histology and protein composition with a fibro-collagenous component varying from sample to sample but invariably higher in normal tissues as compared with the adjacent tumor. These differences involved the need to calculate the repair activities of tissues on the basis of cellular DNA content for comparison purposes. After doing so, tumor and normal tissues exhibited similar abasic site repair capacities, whereas lymphocytes showed a repair capacity significantly lower than tissues. We conclude that early onset sporadic breast cancer patients show no evident defect in repair of abasic sites at the level of both lymphocytes and tumor.

Adult↗
PubMed2000

Efficient DNA base excision repair in ataxia telangiectasia cells.

Ataxia telangiectasia (A-T) cells are sensitive to a broad range of free-radical-producing and alkylating agents. Damage caused by such agents is in part repaired by base excision [base excision repair (BER)]. Two BER pathways have been demonstrated in mammalian cells: a single-nucleotide-insertion pathway and a long-patch pathway involving resynthesis of 2-10 nucleotides. Although early studies failed to detect DNA-repair defects in A-T cells exposed to ionizing radiation and radiomimetic agents, more recent experiments performed in non-dividing A-T cells and the demonstrated interaction of the A-T-mutated protein (ATM) with the BRCA1 gene product suggest that a DNA-repair defect may underlie, at least in part, the radiation sensitivity in A-T cells. We have analysed BER of a single abasic site or a single uracil in two A-T families, using an in vitro BER system. In both families, the mutation involved was homozygous and completely inactivated the ATM protein. No difference was observed between affected individuals and heterozygous or homozygous wild-type relatives in their capacity to perform DNA repair by either one-nucleotide insertion or the long-patch pathway. Hence, the putative DNA-repair defect in A-T cells, if any, does not involve BER.

Ataxia Telangiectasia↗
PubMed1999

Age-independency of AP site incision capacity in women.

Women in the age range 40-59 years have a >4 fold higher risk to develop cancer as compared to women in the age range birth-39 years. This age-related increase in cancer incidence might be partially linked to reduced efficiency of the DNA repair machinery. We have investigated the abasic (AP) site incision capacity of peripheral blood lymphocytes (PBL) from 23 women in the age range 27-57 years. The AP sites incision capacity was determined in relation to protein or DNA content of PBL extracts. In either case, no significant correlation was found between AP sites incision capacity and age, thus suggesting that no decline occurs in the age range investigated.

Adult↗
PubMed1998

Effects of long-term inhaled corticosteroids on skin collagen synthesis and thickness in asthmatic patients.

There are only a few studies on the adverse effects of inhaled corticosteroids on the skin in asthmatic patients. Therefore, we evaluated the effect of inhaled corticosteroids on de novo collagen synthesis of skin and bone, skin thickness and the total amount of skin collagen. Twenty seven consecutive new asthmatic patients, on a moderate dose of budesonide or beclomethasone dipropionate, were invited to take part in this prospective study. Radioimmunological analyses of aminoterminal propeptides of type I and III procollagens (PINP, PIIINP, respectively) in suction blister fluid (SBF) of skin and in serum and carboxyterminal propeptide of type I procollagen (PICP) and cross-linked carbox terminal telopeptide of type I collagen (ICTP) in serum were performed at entry and after 3 and 6 months of inhaled corticosteroid treatment. Ultrasound measurements of skin thickness at two sites were performed at entry, at 3 and 6 months and after 1-2 yrs of inhaled corticosteroid treatment in 20 patients, six of whom had been prescribed one or more courses of oral corticosteroids. Skin hydroxyproline of punch biopsies was determined to measure the total amount of skin collagen (males, at entry and at 6 months). Skin thickness and the total amount of skin collagen on the abdomen were unchanged after 1-2 yrs of inhaled corticosteroid use. A slight decrease was observed in the upper arm skin thickness, especially in those subjects who had received inhaled plus oral corticosteroids. The procollagen propeptide concentrations (PINP, PIIINP) were markedly decreased in SBF at 3 months and remained at this level at 6 months. In serum, a slight decrease was seen in the PINP, PIIINP and ICTP concentrations at 3 and 6 months. In conclusion, inhaled corticosteroids decrease the collagen synthesis of skin and bone, but skin thickness and the total amount of collagen in skin are not changed markedly after 1-2 yrs of treatment.

Administration, Inhalation↗
PubMed1997

Helical CT in evaluation of the bronchial tree.

PURPOSE: To establish a protocol for and to assess the value of helical CT in the imaging of the bronchial tree. MATERIAL AND METHODS: Noncontrast helical CT was performed in 30 patients undergoing fiberoptic bronchoscopy for different reasons. Different protocols were compared; they included overlapping 10 mm, 5 mm, or 3 mm slices and non-tilted, cephalad or caudad tilted images. Ordinary cross-sectional and multiplanar 2D reformats were applied for visualization of the bronchial branches. The effect of increasing the helical pitch was tested in one patient. RESULTS: A total of 92.1-100% of the segmental bronchi present in the helical acquisitions were identified by the different protocols. The collimation had no significant impact on the identification of the bronchial branches, but utilization of 3-mm overlapping slices made it easier to distinguish the nearby branches and provided better longitudinal visualization of the bronchi in 2D reformats. The tilted scans illustrated the disadvantage of not covering all segmental bronchi in one breath-hold. An increase of the pitch from 1 to 1.5 did not cause noticeable blurring of the images. CT and bronchoscopic findings correlated well in the area accessible to bronchoscopy, but CT detected 5 additional pathological lesions (including 2 cancers) in the peripheral lung. CONCLUSION: Helical CT supplemented with bronchography-like 2D reformats provides an effective method complementary to bronchoscopy in the examination of the bronchial tree.

Adult↗
PubMed1997

[Bronchial asthma: pathogenetic mechanisms and genetic aspects].

At present there is a general consensus on the inflammatory nature of bronchial asthma. The main immunological features of the atopic state are represented by the ongoing expansion of Th2-like cells and production of IgE antibodies. IL-4 seems to represent the key factor for the differentiation of Th2-like cells, even though other cytokines have been recently proposed to play a some role. The possible genetic alterations which lead to the deregulated overexpression of IL-4 gene and of other genes of the same family in atopics are under active investigation. The existence of a polymorphism at level of IL-4 gene distal and proximal promoter has directly been shown. Even though IL-4 is required for the development and maintenance of atopic state, IL-5 certainly plays an essential role in the pathogenesis of bronchial inflammation in atopic, intrinsic and occupational asthma. On the basis of the findings emerged from new experimental models, it appears that there are different pathways by which T cell responses can develop bronchial eosinophilic inflammation but all the pathways have to lead to obligatory ongoing production of IL-5. The future research can be also addressed either to clarify the cytokines and/or other factors able to induce the differentiation and ongoing expansion of T cells prevalently producing IL-5, possibly involved in the pathogenesis of intrinsic asthma, either to understanding the nature of stimuli acting as etiologic factors. On the basis of the present acquisitions, IL-5 could represent the most important target of the new approaches to asthma therapy.

Animals↗
PubMed1996

Two pathways for base excision repair in mammalian cells.

Abasic sites (apurinic/apyrimidinic, AP sites) are the most common DNA lesions generated by both spontaneous and induced base loss. In a previous study we have shown that circular plasmid molecules containing multiple AP sites are efficiently repaired by Chinese hamster extracts in an in vitro repair assay. An average patch size of 6.6 nucleotides for a single AP site was calculated. To define the exact repair patch, a circular DNA duplex with a single AP site was constructed. The repair synthesis carried out by hamster and human cell extracts was characterized by restriction endonuclease analysis of the area containing the lesion. The results indicate that, besides the repair events involving the incorporation of a single nucleotide at the lesion site, repair synthesis occurred also 3' to the AP site and involved a repair patch of approximately 7 nucleotides. This alternative repair pathway was completely inhibited by the presence in the repair reaction of a polyclonal antibody raised against human proliferating cell nuclear antigen. These data give the first evidence that mammalian cell extracts repair natural AP sites by two distinct pathways: a single nucleotide gap filling reaction targeted at the AP site and a proliferating cell nuclear antigen-dependent pathway that removes a short oligonucleotide containing the abasic site and 3'-flanking nucleotides.

Animals↗
PubMed1994

Repair of abasic sites by mammalian cell extracts.

Hamster cell extracts that perform repair synthesis on covalently closed circular DNA containing pyrimidine dimers, were used to study the repair of apurinic/apyrimidinic (AP) sites and methoxyamine (MX)-modified AP sites. Plasmid molecules were heat-treated at pH 5 and incubated with MX when required. The amount of damage introduced ranged from 0.2 to 0.9 AP sites/kb. Extracts were prepared from the Chinese hamster ovary CHO-9 cell line and from its derivative, 43-3B clone which is mutated in the nucleotide excision repair (NER) ERCC1 gene. AP and MX-AP sites stimulated repair synthesis by CHO-9 cell extracts. The level of synthesis correlated with the number of lesions and was of similar magnitude to the repair stimulated by 4.3 u.v. photoproducts/kb. Repair of AP and MX-AP sites was faster than the repair of u.v. damage and was independent of ERCC1 gene product. The high level of repair replication was due to a very efficient and rapid incision of plasmids carrying AP or MX-AP sites, performed by abundant AP endonucleases present in the extract. The calculated average repair patch sizes were: 7 nucleotides per AP site; 10 nucleotides per MX-AP site; 28 nucleotides per (6-4) u.v. photoproduct or cyclobutane pyrimidine dimer. The data indicate that AP and MX-AP sites are very efficiently repaired by base-excision repair in mammalian cells and suggest that MX-AP sites may also be processed via alternative repair mechanisms.

Animals↗
PubMed1992

Effect of topoisomerase poisoning by antitumor drugs VM 26, fostriecin and camptothecin on DNA repair replication by mammalian cell extracts.

A recently developed in vitro excision-repair system was used to investigate the effect of the topoisomerase poisons VM 26, fostriecin and camptothecin on DNA repair replication carried out by Chinese hamster ovary cell extracts. VM 26 and camptothecin partially inhibit topoisomerases II and I respectively, which are present in the repair-competent extracts, but have only slight effects on the repair efficiency. On the contrary, the antitumor drug fostriecin markedly affects repair replication but, in contrast to a previous report, does not seem to have, under the experimental conditions used, any inhibitory effect on topoisomerase II. This lack of correlation between the ability to inhibit DNA topoisomerases and the effect on DNA repair replication suggests that topoisomerases should not play a primary role in mammalian excision repair. The use of cleavable-complex stabilizing poisons to investigate the role of eukaryotic topoisomerases in DNA excision repair is discussed.

Alkenes↗