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Biomedical subjects

A Mantovani

Publications and source records attributed to A Mantovani.

At least 19 recordsLinked to original sources
PubMed2006

Overexpression of a member of the pentraxin family (PTX3) in human soft tissue liposarcoma.

A unique feature of human soft tissue liposarcoma is a stable (12;16)(q13;p11) translocation observed mainly in myxoid and roundcell liposarcomas. This translocation results in FUS/CHOP fusion transcripts with a corresponding oncogenic protein. We hypothesised that genes downstream of FUS/CHOP might serve as attractive candidates for novel tumour associated antigens. Among a panel of analysed genes, only pentraxin related gene (PTX3) demonstrated high expression in liposarcomas as compared to normal tissues. The analysis of RNA and protein expression demonstrated concordant results. However, the level of RNA and protein overexpression did not correlate in all cases. Finally, PTX3 expression was not related to presence of a FUS/CHOP fusion transcript within the liposarcoma tissues. PTX3 has been associated with adipocyte differentiation and now, additionally, is characterised by a markedly increased expression in human soft tissue liposarcoma. This finding mandates further research efforts to clarify the exact role of PTX3 in liposarcoma oncogenesis.

Adult↗
PubMed2006

The possible role of endocrine disrupting chemicals in the aetiology of cryptorchidism and hypospadias: a population-based case-control study in rural Sicily.

Abstract This was an open case-control study of the possible association between parental occupational and domestic exposures to potential endocrine disrupting chemicals (EDC) assessed by questionnaire and cryptorchidism and hypospadias in their offspring in the agricultural area of Ragusa. Cases of infants born between 1998 and 2002 with either of these two malformations (n=90), and controls (n=203), were recruited through the paediatric services (for cases) and a random sample of healthy infants attending the same services born in the same period of time (for controls). Data on occupational and environmental exposures of parents prior to and during the index case (or control), were collected through interviews with both parents. Concerning occupational exposures, we did not find a statistically significant increase in risk among parents directly involved in agricultural work. We did find a non-statistically significant increase in risk for cryptorchidism in mothers employed in agriculture [adjusted odds ratios (OR) 2.97; 95% confidence interval (CI) 0.77-11.47] and with probable exposure to pesticides (adjusted OR 2.74; 95% CI 0.72-10.42). Fathers who had indirect contact with agricultural products (transport and retail) had an increased risk (not statistically significant) for cryptorchidism (adjusted OR 2.45; 95% CI 0.63-9.59) and hypospadias and cryptorchidism combined (adjusted OR 2.24; 95% CI 0.67-7.48). Increases in risk of the two malformations pooled were also observed in relation to the mother's age below 25 (adjusted OR 1.99; 95% CI 0.97-4.09), to the presence of genital disease of the father (adjusted OR 2.41; 95%C I0.94-6.17), and the mother (adjusted OR 3.47;95% CI 1.34-8.99), to low birth weight of the infant (adjusted OR 4.49; 95% CI 1.23-16.31). Increased risk was also observed for mothers consuming alcohol during pregnancy (adjusted OR 3.09; 95% CI 0.98-9.66), and for couples who conceived while using condoms (adjusted OR 2.12; 95% CI 1.02-4.41). The study therefore provides only limited support to the hypothesis of a possible association between the risk of cryptorchidism and hypospadias and the occupational exposure to EDC and agricultural work.

Adult↗
PubMed2006

Cryptorchidism and hypospadias in the Sicilian district of Ragusa and the use of pesticides.

The aim of the study was to explore the role of environmental exposures to pesticides in the birth prevalence of hypospadias and cryptorchidism, in the 12 agricultural municipalities of Ragusa Sicily. Data on the birth prevalence of the two birth defects were obtained from the local pediatric services for the period 1998-2002. Municipalities were ranked according to the degree of "pesticide impact" on the basis of three quantitative criteria of intensity of agricultural activities of the population. We found a significantly higher birth prevalence of hypospadias with increasing "pesticide impact" (trend test, P=0.003). The association with cryptorchidism was not statistically significant, but when the two birth defects were pooled together, the linear trend was significant (trend test, P=0.001).

Abnormalities, Multiple↗
PubMed2006

The chemoattractant decoy receptor D6 as a negative regulator of inflammatory responses.

Other than signalling receptors sustaining leucocyte recruitment during inflammatory reactions, the chemokine system includes 'silent' receptors with distinct specificity and tissue distribution. The best-characterized molecule of this subgroup is the CC chemokine receptor D6, which binds most inflammatory CC chemokines and targets them to degradation via constitutive ligand-independent internalization. Structure-function analysis and recent results with gene-targeted animals indicate that D6 has unique functional and structural features, which make it ideally adapted to act as a chemokine decoy and scavenger receptor, strategically located on lymphatic endothelium and placenta to dampen inflammation in tissues and draining lymph nodes.

Humans↗
PubMed2005

The presence of functional mannose receptor on macrophages at the maternal-fetal interface.

BACKGROUND: The mannose receptor (MR) is involved in the initiation of the immune response and regulation of homeostasis during inflammation and tissue remodeling. METHODS: Distribution, endocytosis and possible natural ligand tumor associated glycoprotein-72 (TAG-72) for the MR have been examined by immunohistology, immunocytochemistry and flow cytometry at the maternal-fetal interface, characterized by extensive tissue remodeling. RESULTS: Contrary to disseminated distribution of the MR positive (MR+) cells in term placenta, the MR+ cells of early pregnancy decidua intimately surrounded glands and followed tissue distribution of CD14 positive cells. The mannose receptor was present on freshly isolated first trimester decidual mononuclear cells and distributed mostly on macrophages (77.08 +/- 10.55%, mean +/- SD). The expression of the MR on CD14 positive cells decreased following 18 h culture (P < 0.01) and was accompanied by the reduction of fluorescein isothiocyanate (FITC)-dextran uptake. PAM-1 anti-MR antibody, mannan and TAG-72 reduced FITC-dextran uptake by decidual macrophages. CONCLUSIONS: These data indicate that the MR+ macrophages, surrounding early decidual glands, are able to internalize ligands for carbohydrate recognition domain of the receptor, including decidual secretory phase mucin TAG-72.

Antigens, Neoplasm↗
PubMed2004

PTX3 function as an opsonin for the dectin-1-dependent internalization of zymosan by macrophages.

Pentraxin 3 (PTX3) is a tumor necrosis factor and interleukin-1beta-stimulated gene that encodes a long PTX with proinflammatory activity. Here, we show that peritoneal macrophages derived from PTX3 transgenic (Tg) mice express higher levels of PTX3 mRNA than macrophages from wild-type (WT) mice, at basal level as well as upon stimulation with zymosan (Zy). Macrophages from Tg mice also showed improved opsonin-independent phagocytosis of Zy particles and the yeast form of the fungus Paracoccidioides brasiliensis. In the case of P. brasiliensis, an enhanced microbicidal activity accompanied by higher production of nitric oxide was also observed in macrophages from Tg mice. Using fluorescein-activated cell sorter analysis and reverse transcriptase-polymerase chain reaction, we demonstrated that basal level of Toll-like receptor-6 and Zy-induced dectin-1 expression was slightly but consistently higher in macrophages from Tg mice than in macrophages from WT mice. Recombinant (r)PTX3 protein binds to Zy particles as well as to yeast cells of P. brasiliensis and addition of rPTX3, to a culture of WT-derived macrophages containing Zy leads to an increase in the phagocytic index, which parallels that of Tg-derived macrophages, demonstrating the opsonin-like activity of PTX3. It is important that blockade of dectin-1 receptor inhibited the phagocytosis of Zy particles by WT and PTX3 Tg macrophages, pointing out the relevant role of dectin-1 as the main receptor involved in Zy uptake. Our results provide evidence for a role of PTX3 as an important component of the innate-immune response and as part of the host mechanisms that control fungal recognition and phagocytosis.

Animals↗
PubMed2004

Effect of inflammatory attacks in the classical type hyper-IgD syndrome on immunoglobulin D, cholesterol and parameters of the acute phase response.

BACKGROUND: Classical type hyper-immunoglobulin D (IgD) syndrome (HIDS) is an hereditary auto-inflammatory disorder, characterized by recurrent episodes of fever, lymphadenopathy, abdominal distress and a high serum concentration of IgD. It is caused by mevalonate kinase deficiency. OBJECTIVE: To further characterize the acute phase response during fever attacks in HIDS in order to improve diagnosis. SUBJECTS: Twenty-two mevalonate kinase-deficient HIDS patients. METHODS: Blood samples were drawn during and in between febrile attacks, and concentrations ofC-reactive protein (CRP), ferritin, procalcitonin, pentraxin 3, IgD and cholesterol in several lipoprotein fractions were determined. RESULTS: The marked acute phase response at the time of a fever attack in classical type HIDS is reflected by a rise in CRP accompanied by a moderate but statistically significant rise in procalcitonin and pentraxin 3. In only two of 22 patients, procalcitonin concentration rose above 2 ng mL(-1) during fever attack, compatible with the noninfectious nature of these attacks. Ferritin does not reach the high concentrations found in adult-onset Still's disease. Despite the defect in mevalonate kinase, a component of cholesterol metabolism, serum cholesterol did not change during attacks. IgD concentration is elevated regardless of disease activity, although there is appreciable variation during life. Its role in HIDS remains unclear. CONCLUSION: The combination of high CRP concentration plus procalcitonin concentration <2 ng mL(-1) in a symptomatic HIDS patient might indicate a febrile attack without (bacterial) infection; this observation warrants further investigation for its usefulness as a marker in clinical practice.

Acute-Phase Reaction↗
PubMed2004

Factors regulating endogenous retroviral sequences in human and mouse.

Endogenous retroviruses (ERVs) are stably integrated in the genome of vertebrates and inherited as Mendelian genes. The several human ERV (HERV) families and related elements represent up to 5-8% of the DNA of our species. ERVs may be involved in the regulation of adjacent genomic loci, especially promoting the tissue-specific expression of genes; some HERVs may have functional roles, e.g., coding for the placental fusogenic protein, syncytin. This paper reviews the growing evidence about factors that may modulate ERVs, including: cell and tissue types (with special attention to placenta and germ cells), processes related to differentiation and aging, cytokines, agents that disrupt cell functions (e.g., DNA hypomethylating agents) and steroids. Special attention is given to HERVs, due to their possible involvement in autoimmunity and reproduction, as well as altered expression in some cancer types; moreover, different HERV families may deserve specific attention, due to remarkable differences concerning, e.g., expression in tissues. A comparison with factors interacting with murine ERV-related sequences indicates that the mouse may be a useful model for studying some patterns of HERV regulation. Overall, the available evidence identifies the diverse, potential interactions with endogenous or exogenous factors as a promising field for investigating the roles of ERVs in physiology and disease.

Animals↗
PubMed2004

[Celiac disease and its endocrine and nutritional implications on male reproduction].

The problem of the interference of celiac disease (CD) with the male reproductive system is made evident both by the recognized adverse effects on female reproduction and by the multifactorial nature of the disease. It is important to consider CD as a multifactorial condition since its diverse effects can be modulated, besides gluten, by different concurrent genetic and environmental factors. The male CD patient has a greater risk of infertility and other reproductive disturbances, as well as a greater incidence of hypoandrogenism. In this paper the problems of CD associated to endocrine disorders and to deficiencies of micronutrients are discussed. Affected males show a picture of tissue resistance to androgens. Moreover, attention should be paid to increases of FSH and prolactin; these are not associated to infertility and/or impotence, but they may indicate an imbalance at hypothalamus-pituitary level, with general effects on health: an example is the increased risk of male osteoporosis in CD patients. Hormone alterations are reversible upon start of the gluten-free diet, emphasizing the importance of early diagnosis; this should be performed in the case of clinical suspicion, e.g., unexplained hypoandrogenism. As regards nutritional aspects, the folic acid deficiency of CD can affect rapidly proliferating tissues, such as the embryo and the seminiferous epithelium. More attention should be paid to deficiencies of fat-soluble vitamins, such as A and E, observed in CD. Vitamin A is important for Sertoli cell function as well as for early spermatogenetic phases. Vitamin E supports the correct differentiation and function of epidydimal epithelium, spermatid maturation and secretion of proteins by the prostate. Therefore, CD male patients should be considered as vulnerable subjects; thus, the detection of early biomarkers of andrological or endocrinological dysfunctions should trigger timely strategies for prevention and treatment.

Celiac Disease↗
PubMed2004

Notes on cystic echinococcosis in the Mediterranean.

Cystic Echinococcosis (CE), caused by Echinococcus granulosus, is present from the beginning of history and in the Mediterranean it is linked to the dog-sheep cycle. The Mediterranean area possesses many features favouring CE. Positive and negative influences derived from the action of the European Community and from recent developments. The control measures of CE have political, economic, public health and environmental implications. Dog population and dog-transmitted zoonoses control, improvement of slaughtering procedures and the destruction of infected viscera, health education, interprofessional cooperation are able individually to constitute a contraposition to CE and combined to compose a control program. Epidemiological surveillance and control of CE in the Mediterranean are coordinated by the WHO Mediterranean Zoonoses Control Centre of Athens.

Animals↗
PubMed2002

Cystic echinococcosis and the Mediterranean Region: a long-lasting association.

Cystic echinococcosis (CE) is an important zoonosis in Italy and in the whole Mediterranean Region, as confirmed by the work by Ettore Biocca, whose contributions to the subject are reported in a summarised annex to the bibliography. The contribution to the understanding and control of CE are presented, with special emphasis on the socio-economic impact, on factors affecting the maintenance of CE in the Mediterranean Region, on the epidemiological situation and control measures, on the present status of epidemiological surveillance, on the control problems in normal and emergency situations, on health education and training. Also, the justifications of combined control programmes are discussed, which may be applied only in situations of peace and well-being.

Animal Husbandry↗
PubMed2002

[Possible animal models of endocrine, immune and reproductive complications of celiac disease].

This paper underlines the need of developing animal models to study the diverse complications of celiac disease (CD). CD is a multifactorial condition requiring both an exogenous element (gluten) and complex genetic factors; moreover, CD is associated to several endocrine, immune and reproductive diseases, whose onset may be influenced by other environmental factors as well. In particular, the intestinal absorption of exogenous factors may be important for the outcome of CD as well as of the associated diabetes and/or thyroiditis. Presently, there are no adequate animal models for the systemic complications of CD; in particular, there are no gene knock-out models. However, models are available as regards either gluten enteropathy, such as Irish Setter and Balb/c e BDF1 mouse strains, and endocrine-immune diseases associated with CD, such as BB rats and NOD mice. A deeper exploitation of the available models could provide important information on the factors modulating intestinal permeability, the pathogenesis of extraintestinal alterations and the interactions between gluten and other metabolic, nutritional and environmental factors. The elaboration of in vivo models requires a sound basis of knowledge at molecular level, as well as the modulation of the metabolic alteration through relevant exogenous factors, first of all the dietary assumption of gluten. Therefore, the availability of experimental models may provide significant advances on the prevention and treatment, allowing a complete analysis of affected organisms as well as the use of pharmacological and/or immune stimuli; more information may be also derived on the possible long-term effects of gluten traces in CD-affected subjects, thus reducing the need for lengthy clinical studies.

Animals↗
PubMed2002

Endocrine effects in the hazard assessment of drugs used in animal production.

Criteria of toxicological assessment are currently reviewed to ensure an adequate protection to susceptible groups, such as infants and children; in particular, concern arises about altered endocrine homeostasis in the developing organism, eliciting possible persistent effects such as reproductive disturbances and increased risk of tumours in target organs. Such items are obviously relevant also for veterinary drugs, whose main safety issue is potential lifetime exposure to residues. Two groups of chemicals, nitroimidazoles and imidazole antifungals, are reviewed as examples of the relevance of endocrine toxicity to the hazard assessment of compounds used in animal production. Nitroimidazoles are metabolized into genotoxic intermediates; in rodents they induce testicular toxicity and carcinogenicity. In particular, mammary neoplasms, mostly fibroadenomas, are consistently induced in rats as the most important effect in chronic studies; this may hint to possible endocrine-related mechanisms. Accordingly, evidences on other chemicals (e.g., triazines) show mammary tumorigenicity in rodents associated to hormonal alterations. In fact, nitroimidazoles affect synthesis of both pituitary and steroid hormones in vitro and rise progesterone and FSH levels in rats; also, limited clinical data in humans indicate endocrine-related effects. Overall, nitroimidazoles appear to affect the endocrine balance; however, the actual importance of such alterations, especially in regards to rat mammary tumours, has yet to be clarified. Imidazole antimycotics are broad-spectrum inhibitors of steroid synthesis; accordingly, diverse reproductive and developmental alterations are observed, depending on age and sex of animals exposed. Effects include pregnancy loss, delayed pup growth as well as reduced weight of androgen-dependent tissue; however, it is still difficult to identify the most susceptible biological phase. Overall the potential for inducing endocrine-related alterations should be carefully evaluated also for drugs used in animal production. A screening battery should produce a distinct fingerprint for each major endocrine activity, thus targeting longer-term tests (such as the two-generation study) on the most relevant endpoints. Moreover, the validation of molecular approaches would contribute to a biologically-based evaluation, by providing insights on such items as early effects and species-specificity.

Animal Experimentation↗
PubMed2001

Selective induction of phospholipase D1 in pathogen-activated human monocytes.

Phospholipase D (PLD) activation is part of the complex signalling cascade induced during phagocyte activation. Two PLD isoforms have been cloned, but their role in phagocyte functions is still poorly defined. We report that resting fresh circulating human monocytes expressed PLD1. PLD1 protein expression was rapidly down-regulated during cell culture. Lipopolysaccharide and pathogen-derived agonists (Candida albicans, arabinoside-terminated lipoarabinomannan and Gram-positive bacteria, but not mannose-capped lipoarabinomannan or double-stranded RNA) strongly induced PLD1 expression at both the mRNA and protein levels. Pro-inflammatory cytokines [interleukin (IL)-1beta and tumour necrosis factor alpha] had only a weak effect, whereas immune cytokines (IL-6 and interferon gamma), anti-inflammatory cytokines (IL-13 and IL-10) and chemoattractants (fMet-Leu-Phe and macrophage chemoattractant protein 1) were inactive. None of the agonists tested induced significant changes in the basal expression of PLD2 mRNA. Consistent with PLD1 up-regulation was the observation that PLD enzymic activity was higher in monocytes treated with active-pathogen-derived agonists than in control cells, when stimulated with PMA or with chemotactic agonists (fMet-Leu-Phe and C5a). Thus PLD2 seems to be a constitutive enzyme in circulating monocytes. Conversely, PLD1 is an inducible protein, rapidly regulated during culture conditions and selectively induced during cell activation. Therefore PLD1 might have a relevant role in immune responses against pathogens and in chronic inflammation.

Blotting, Northern↗
PubMed2001

Chemoattractants MDC and TARC are secreted by malignant B-cell precursors following CD40 ligation and support the migration of leukemia-specific T cells.

The use of tumor cells as vaccines in cancer immunotherapy is critically dependent on their capacity to initiate and amplify tumor-specific immunity. Optimal responses may require the modification of the tumor cells not only to increase their immunogenicity but also to improve their ability to recruit effector cells to the tumor sites or sites of tumor antigen exposure. It has been reported that CD40 cross-linking of acute lymphoblastic leukemia (ALL) cells significantly increases their immunogenicity and allows the generation and expansion of autologous antileukemia cytotoxic T lymphocytes. This study demonstrates that the CD40 ligation of these tumor cells also induces the secretion of the CC-chemokines MDC and TARC. Supernatants from malignant cells cultured in the presence of sCD40L promote the migration of activated T cells that express CCR4, the common specific receptor for MDC and TARC. More importantly, the supernatants from CD40-stimulated tumor cells also support the transendothelial migration of autologous CCR4(+) antileukemia T cells. Therefore, the results demonstrate that the delivery to leukemia cells of a single physiologic signal, that is, CD40 cross-linking, simultaneously improves tumor cell immunogenicity and induces potent chemoattraction for T cells. (Blood. 2001;98:533-540)

Antigen Presentation↗