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Biomedical subjects

A Vicari

Publications and source records attributed to A Vicari.

At least 19 recordsLinked to original sources
PubMed2003

What's new in the field of cancer vaccines?

The observation that in some cases tumors undergo spontaneous regression concomitantly with autoimmune manifestations has been interpreted as an indication of the involvement of the immune system in tumor rejection. This raised the conceptual possibility that the immune system could be used against the tumor. However, since tumor cells are poorly immunogenic by themselves, early attempts to develop immune-based approaches for cancer therapy saw the use of tumor cells transduced with genes coding for cytokines or costimulatory molecules to enhance in vivo immunity. The identification of cytotoxic T lymphocyte (CTL)-defined tumor-associated antigens has allowed the development of new strategies for cancer immunotherapy. Novel adjuvants have been identified, and different modes of antigen delivery were devised which aim at inducing efficient CTL responses in patients. This review will discuss some of what is currently considered as relevant aspects of antitumor immunization.

Antigens, Neoplasm↗
PubMed2001

Mouse type I IFN-producing cells are immature APCs with plasmacytoid morphology.

We show here that mouse interferon-alpha (IFN-alpha)-producing cells (mIPCs) are a unique subset of immature antigen-presenting cells (APCs) that secrete IFN-alpha upon stimulation with viruses. mIPCs have a plasmacytoid morphology, can be stained with an antibody to Ly6G and Ly6C (anti-Ly6G/C) and are Ly6C+B220+CD11cloCD4+; unlike other dendritic cell subsets, however, they do not express CD8alpha or CD11b. Although mIPCs undergo apoptosis in vitro, stimulation with viruses, IFN-alpha or CpG oligonucleotides enhanced their survival and T cell stimulatory activity. In vivo, mIPCs were the main producers of IFN-alpha in cytomegalovirus-infected mice, as depletion of Ly6G+/C+ cells abrogated IFN-alpha production. mIPCs produced interleukin 12 (IL-12) in response to viruses and CpG oligodeoxynucleotides, but not bacterial products. Although different pathogens can selectively engage various APC subsets for IL-12 production, IFN-alpha production is restricted to mIPCs' response to viral infection.

Animals↗
PubMed2000

Macrophage inflammatory protein 3alpha is expressed at inflamed epithelial surfaces and is the most potent chemokine known in attracting Langerhans cell precursors.

Dendritic cells (DCs) form a network comprising different populations that initiate and differentially regulate immune responses. Langerhans cells (LCs) represent a unique population of DCs colonizing epithelium, and we present here observations suggesting that macrophage inflammatory protein (MIP)-3alpha plays a central role in LC precursor recruitment into the epithelium during inflammation. (a) Among DC populations, MIP-3alpha was the most potent chemokine inducing the selective migration of in vitro-generated CD34(+) hematopoietic progenitor cell-derived LC precursors and skin LCs in accordance with the restricted MIP-3alpha receptor (CC chemokine receptor 6) expression to these cells. (b) MIP-3alpha was mainly produced by epithelial cells, and the migration of LC precursors induced by the supernatant of activated skin keratinocytes was completely blocked with an antibody against MIP-3alpha. (c) In vivo, MIP-3alpha was selectively produced at sites of inflammation as illustrated in tonsils and lesional psoriatic skin where MIP-3alpha upregulation appeared associated with an increase in LC turnover. (d) Finally, the secretion of MIP-3alpha was strongly upregulated by cells of epithelial origin after inflammatory stimuli (interleukin 1beta plus tumor necrosis factor alpha) or T cell signals. Results of this study suggest a major role of MIP-3alpha in epithelial colonization by LCs under inflammatory conditions and immune disorders, and might open new ways to control epithelial immunity.

Animals↗
PubMed2000

Dendritic cell biology and regulation of dendritic cell trafficking by chemokines.

DC (dendritic cells) represent an heterogeneous family of cells which function as sentinels of the immune system. They traffic from the blood to the tissues where, while immature, they capture antigens. Then, following inflammatory stimuli, they leave the tissues and move to the draining lymphoid organs where, converted into mature DC, they prime naive T cells. The key role of DC migration in their sentinel function led to the investigation of the chemokine responsiveness of DC populations during their development and maturation. These studies have shown that immature DC respond to many CC and CXC chemokines (MIP-1 alpha, MIP-1 beta, MIP-3 alpha, MIP-5, MCP-3, MCP-4, RANTES, TECK and SDF-1) which are inducible upon inflammatory stimuli. Importantly, each immature DC population displays a unique spectrum of chemokine responsiveness. For examples, Langerhans cells migrate selectively to MIP-3 alpha (via CCR6), blood CD11c+ DC to MCP chemokines (via CCR2), monocytes derived-DC respond to MIP-1 alpha/beta (via CCR1 and CCR5), while blood CD11c- DC precursors do not respond to any of these chemokines. All these chemokines are inducible upon inflammatory stimuli, in particular MIP-3 alpha, which is only detected within inflamed epithelium, a site of antigen entry known to be infiltrated by immature DC. In contrast to immature DC, mature DC lose their responsiveness to most of these inflammatory chemokines through receptor down-regulation or desensitization, but acquire responsiveness to ELC/MIP-3 beta and SLC/6Ckine as a consequence of CCR7 up-regulation. ELC/MIP-3 beta and SLC/6Ckine are specifically expressed in the T-cell-rich areas where mature DC home to become interdigitating DC. Altogether, these observations suggest that the inflammatory chemokines secreted at the site of pathogen invasion will determine the DC subset recruited and will influence the class of the immune response initiated. In contrast, MIP-3 beta/6Ckine have a determinant role in the accumulation of antigenloaded mature DC in T cell-rich areas of the draining lymph node, as illustrated by recent observations in mice deficient for CCR7 or SLC/6Ckine. A better understanding of the regulation of DC trafficking might offer new opportunities of therapeutic interventions to suppress, stimulate or deviate the immune response.

Animals↗
PubMed2000

Comparison of the persistence of atrazine and metolachlor under field and laboratory conditions.

A study was carried out in a loamy soil to evaluate the degradation of atrazine and metolachlor under laboratory-controlled and field-variable conditions as a function of temperature and soil moisture content. In laboratory trials, metolachlor showed fast degradation, with half-lives from 100 to 5.7 days in a temperature range from 5 to 35 degrees C at 100% of field capacity, whereas in the same conditions the degradation rate of atrazine was relatively slow, with half-lives from 407 to 23 days. Modeling of laboratory degradation data to predict field persistence was carried out. Field persistence of atrazine and metolachlor was measured in the same soil during the corn growing seasons in 1993, 1994, and 1996. In the three years the mean half-dissipation times for atrazine and metolachlor were 36 and 21 days, respectively. Calculations from model equations gave acceptable prediction of field dissipation of both herbicides. Limitations and perspectives of employed modelization procedure are discussed.

Acetamides↗
PubMed1999

Regulation of dendritic cell trafficking: a process that involves the participation of selective chemokines.

DC function as sentinels of the immune system. They traffic from the blood to the tissues where, while immature, they capture antigens. They then leave the tissues and move to the draining lymphoid organs where, converted into mature DC, they prime naive T cells. This suggestive link between DC traffic pattern and functions led to the investigation of the chemokine responsiveness of DC during their development and maturation. These studies have shown that immature and mature DC are not recruited by the same chemokines. Immature DC respond to many CC- and CXC-chemokines (MIP-1alpha, MIP-1beta, MIP-5, MCP-3, MCP-4, RANTES, TECK, and SDF-1) and in particular to MIP-3alpha/LARC, which acts through CCR6, a receptor mainly expressed in DC and lymphocytes. Like most other chemokines acting on immature DC, MIP-3alpha is inducible on inflammatory stimuli. In contrast, mature DC have lost their responsiveness to most of these chemokines through receptor down-regulation or desensitization, but acquired responsiveness to MIP-3beta/ELC and 6Ckine/SLC as a consequence of CCR7 up-regulation. MIP-3alpha mRNA is only detected within inflamed epithelial crypts of tonsils, the site of antigen entry known to be infiltrated by immature DC, whereas MIP-3alpha and 6Ckine are specifically expressed in the T cell-rich areas where mature IDC home. These observations suggest a role for chemokines induced on inflammation such as MIP-3alpha in recruitment of immature DC at the site of injury and a role for MIP-3beta/6Ckine in accumulation of antigen-loaded mature DC in T cell-rich areas of the draining lymph node. A better understanding of the regulation of DC trafficking might offer new opportunities of therapeutic interventions to suppress or stimulate the immune response.

Animals↗
PubMed1998

Selective recruitment of immature and mature dendritic cells by distinct chemokines expressed in different anatomic sites.

DCs (dendritic cells) function as sentinels of the immune system. They traffic from the blood to the tissues where, while immature, they capture antigens. They then leave the tissues and move to the draining lymphoid organs where, converted into mature DC, they prime naive T cells. This suggestive link between DC traffic pattern and functions led us to investigate the chemokine responsiveness of DCs during their development and maturation. DCs were differentiated either from CD34(+) hematopoietic progenitor cells (HPCs) cultured with granulocyte/macrophage colony-stimulating factor (GM-CSF) plus tumor necrosis factor (TNF)-alpha or from monocytes cultured with GM-CSF plus interleukin 4. Immature DCs derived from CD34(+) HPCs migrate most vigorously in response to macrophage inflammatory protein (MIP)-3alpha, but also to MIP-1alpha and RANTES (regulated on activation, normal T cell expressed and secreted). Upon maturation, induced by either TNF-alpha, lipopolysaccharide, or CD40L, DCs lose their response to these three chemokines when they acquire a sustained responsiveness to a single other chemokine, MIP-3beta. CC chemokine receptor (CCR)6 and CCR7 are the only known receptors for MIP-3alpha and MIP-3beta, respectively. The observation that CCR6 mRNA expression decreases progressively as DCs mature, whereas CCR7 mRNA expression is sharply upregulated, provides a likely explanation for the changes in chemokine responsiveness. Similarly, MIP-3beta responsiveness and CCR7 expression are induced upon maturation of monocyte- derived DCs. Furthermore, the chemotactic response to MIP-3beta is also acquired by CD11c+ DCs isolated from blood after spontaneous maturation. Finally, detection by in situ hybridization of MIP-3alpha mRNA only within inflamed epithelial crypts of tonsils, and of MIP-3beta mRNA specifically in T cell-rich areas, suggests a role for MIP-3alpha/CCR6 in recruitment of immature DCs at site of injury and for MIP-3beta/CCR7 in accumulation of antigen-loaded mature DCs in T cell-rich areas.

Cell Differentiation↗
PubMed1998

Characterization of a novel CC chemokine, HCC-4, whose expression is increased by interleukin-10.

We have identified and characterized a human beta (CC) chemokine, designated HCC-4, that is most closely related to HCC-1 and which demonstrates chemotactic activity for monocytes. Northern analysis of multiple tissue blots and of activated monocytes mRNA shows expression of a 500-bp mRNA. A 1,500-bp mRNA was highly expressed in monocytes activated 12 hours in the presence of interleukin-10 (IL-10) but was absent in monocytes activated for only 1 hour regardless of the presence or absence of IL-10. The upregulation of expression in the presence of IL-10 is in contrast to the downregulatory effects of IL-10 on expression of most other chemokines. Recombinant HCC-4 demonstrated chemotactic activity for human monocytes and THP-1 monocyte cells but not for resting lymphocytes or neutrophils. HCC-4 also induced a Ca2+ flux in THP-1 cells that was desensitized by prior exposure to RANTES. Taken together, these data indicate that HCC-4 is a novel chemokine whose expression is uniquely upregulated by IL-10.

Amino Acid Sequence↗
PubMed1997

Micellar electrokinetic capillary chromatography as a method for determination of n-octanol/water partition coefficients of pesticides.

Micellar electrokinetic capillary chromatography (MEKC) was used to determine the n-octanol/water partition coefficient (Kow) of nonionic and ionic organic chemicals, mainly herbicides. Three electrolyte buffer systems with different organic modifiers were tested to evaluate their effect on the linear relationship between log Kow and log k'. The effect of the pH value of injected samples on linear log Kow/log k' relationship of ionic chemicals was also evaluated. Since a good correlation was found between log Kow values and the logarithms of the capacity factor (k') of each tested organic solvent, other parameters were considered to evaluate the efficacy of the method, such as the rate of electroosmotic flow, the efficiency and reproducibility of the separation, and the separation number (n). The method was found to be applicable over a range of log Kow values from 0.72 to 5.1 and demonstrated a good predictive capability giving similar results to direct experimental measures, at least within classes of compounds with similar physico-chemical properties.

1-Octanol↗
PubMed1997

Requirement of IL-7 for IL-4-producing potential of MHC class I-selected CD4-CD8-TCR alpha beta+ thymocytes.

IL-7 plays an important role in the growth and differentiation of T cells. We have previously reported that IL-7 induces preferential expansion of MHC class I-selected CD4-CD8-TCR alpha beta+ thymocytes which express a skewed V beta repertoire and are potent IL-4 producers. In this report, we provide evidence that IL-1 in combination with granulocyte macrophage colony stimulating factor can also expand this population. Yet, these cells do not share the functional characteristics of those obtained in the presence of IL-7, i.e. cytotoxic activity and high IL-4 production. These functional capacities can be acquired by adding IL-7. In conclusion, our findings demonstrate that the capacity of MHC class I-selected CD4-CD8-TCR alpha beta+ thymocytes to produce IL-4 as well as to kill target cells is IL-7 dependent.

Animals↗
PubMed1996

Identification of a novel selD homolog from eukaryotes, bacteria, and archaea: is there an autoregulatory mechanism in selenocysteine metabolism?

Escherichia coli selenophosphate synthetase (SPS, the selD gene product) catalyzes the production of monoselenophosphate, the selenium donor compound required for synthesis of selenocysteine (Sec) and seleno-tRNAs. We report the molecular cloning of human and mouse homologs of the selD gene, designated Sps2, which contains an in-frame TGA codon at a site corresponding to the enzyme's putative active site. These sequences allow the identification of selD gene homologs in the genomes of the bacterium Haemophilus influenzae and the archaeon Methanococcus jannaschii, which had been previously misinterpreted due to their in-frame TGA codon. Sps2 mRNA levels are elevated in organs previously implicated in the synthesis of selenoproteins and in active sites of blood cell development. In addition, we show that Sps2 mRNA is up-regulated upon activation of T lymphocytes and have mapped the Sps2 gene to mouse chromosome 7. Using the mouse gene isolated from the hematopoietic cell line FDCPmixA4, we devised a construct for protein expression that results in the insertion of a FLAG tag sequence at the N terminus of the SPS2 protein. This strategy allowed us to document the readthrough of the in-frame TGA codon and the incorporation of 75Se into SPS2. These results suggest the existence of an autoregulatory mechanism involving the incorporation of Sec into SPS2 that might be relevant to blood cell biology. This mechanism is likely to have been present in ancient life forms and conserved in a variety of living organisms from all domains of life.

Amino Acid Sequence↗
PubMed1996

Monitoring of herbicide pollution in water by capillary electrophoresis.

In recent years, capillary electrophoresis (CE) has demonstrated itself to be an extremely powerful analytical technique. However, CE has not yet been fully evaluated for the environmental analysis of herbicides. In this paper, the potential and drawbacks of CE for the separation and detection of herbicides in water sources are outlined. Details are given both on the applicability of CE to trace level monitoring of herbicides in water sources and on its usefulness in studies regarding the environmental behaviour of herbicides in water systems.

Chromatography, High Pressure Liquid↗
PubMed1996

IL-7 reverses NK1+ T cell-defective IL-4 production in the non-obese diabetic mouse.

Converging data suggest an important role for IL-7 in T lymphocyte maturation as illustrated by the severe T lymphopenia observed in IL-7-deficient mice. We recently reported that IL-7 preferentially promotes the in vitro expansion of a discrete MHC class I-dependent lymphocyte subset comprising both CD4+ and CD4-CD8- TCR alpha beta + cells bearing several NK cells markers such NK1.1 and Ly-49. These T cells, designated as NK1+ T cells, have the unique property among thymocytes of producing large amounts of IL-4 upon primary stimulation via the TCR. We have further demonstrated that thymic NK1+ T cells of non-obese diabetic (NOD) mice, a spontaneous model of autoimmune type I diabetes, are markedly deficient in maturation both quantitatively and functionally (IL-4 production). In the present experiments, the addition of exogenous IL-7 completely restored IL-4 production by anti-TCR alpha beta-stimulated mature (HSA-CD8-) thymocytes in NOD mice. A short 2 h preincubation with IL-7 was sufficient to restore both the expression of IL-4 mRNA and IL-4 production capacity. This was related to a direct effect on NK1+ thymocytes since: (i) the effect of IL-7 was restricted to the non-mainstream MEL-14- 3G11- TCR alpha beta + subset which mostly concentrates the IL-4-producing capacity and (ii) IL-7 did not restore IL-4 production in class I-deficient mice which lack the NK1+ T cell subset. Importantly, this activity of IL-7 on NK1+ T cells was also demonstrated in non-autoimmune strains of mice. These results were extended in vivo by showing that the IL-7 treatment significantly increased the anti-CD3 triggered IL-4 production by NK1+ T spleen cells. These findings confirm the role of IL-7 in NK1+ T cell maturation and suggest that the NK1+ T cell defect in NOD mice could be related to insufficient intrathymic IL-7 bioavailability.

Animals↗
PubMed1995

MHC class I-selected CD4-CD8-TCR-alpha beta+ T cells are a potential source of IL-4 during primary immune response.

Differentiation of naive CD4+ lymphocytes into either Th1 or Th2 cells is influenced by the cytokine present during initial Ag priming. IL-4 is the critical element in the induction of Th2 response; however, its origin during a primary immune response is not well defined. In the present study, we characterized a novel potential source of IL-4, the class I-selected CD4-CD8-TCR-alpha beta+ T cells. In a first set of experiments, we demonstrated that CD4-CD8-TCR-alpha beta+ thymocytes produce a large amount of IL-4 after in vitro anti-CD3 stimulation. This phenomenon was not observed in class I-deficient mice, demonstrating that among these cells, the class I-selected subset was predominantly responsible for IL-4 production. Further studies focused on the in vivo IL-4-producing capacity of peripheral CD4-CD8-TCR-alpha beta+ T cells. To this end, a single injection of anti-CD3 mAb, which promptly induces IL-4 mRNA expression, was used. Peripheral CD4-CD8-TCR-alpha beta+ T cells express high levels of IL-4 mRNA in response to in vivo anti-CD3 challenge. Furthermore, analysis performed in mice lacking MHC class I or class II molecules demonstrates that both the class I-selected subset of CD4-CD8-TCR+ and CD4+ peripheral T lymphocytes are the major IL-4 producers after in vivo anti-CD3 stimulation. These findings suggest that class I-selected CD4-CD8-TCR-alpha beta+ and CD4+ T cell populations are important sources of IL-4 probably implicated in the development of specific Th2 immune responses.

Animals↗
PubMed1995

Surveillance of contagious bovine pleuropneumonia in Switzerland.

An active surveillance system for contagious bovine pleuropneumonia (CBPP) has been established in Switzerland. The system is based on the detection of typical gross pathological lesions in the lungs of slaughtered cattle, followed by microbiological analysis of the sampled organs and sero-epidemiological investigation of the herd of origin for each suspect case. The programme was tested over six months. The prevalence of lung lesions detected in carcasses during this period in the 108 participating abattoirs was 0.04%, but Mycoplasma mycoides subsp. mycoides SC was not isolated from any of these organs. On the basis of the results presented, there is no evidence of CBPP in Switzerland. The surveillance programme will continue, however, in order to document the situation and eventually obtain a disease-free status in accordance with international standards.

Abattoirs↗
PubMed1995

[The epidemiology of contagious lung disease in Switzerland].

Although contagious bovine pleuropneumonia (CBPP) has not been diagnosed in Switzerland since 1895, anti-CBPP antibodies were detected in several cattle that had been imported from Switzerland to Italy. In order to clarify the current disease situation in Switzerland, detailed epidemiological investigations were performed, including the control of 200,000 slaughter cattle in 108 abattoirs and serological testing of more than 2200 animals from 134 farms. The data collected in the slaughterhouses showed a prevalence of suspect lung lesions of 0.04%. Yet, the causing agent of CBPP Mycoplasma mycoides subsp. mycoides SC could not be isolated from any of these 84 microbiologically analysed lungs. On the other hand, up to 3.5% positive results were obtained from the serological tests. These results are most probably caused by cross-reactions of other mycoplasma. Based on these data Switzerland is still to be considered free of CBPP. Nevertheless, a continued surveillance programme including routine checks of all cattle carcasses at the abattoir and subsequent epidemiological investigation of suspect cases are recommended.

Animals↗
PubMed1995

Radiographic modalities for diagnosis and treatment planning in implant dentistry.

Early in the development of implant technology it became apparent that conventional dental imaging techniques were limited for evaluating patients for implant surgery. During the treatment planning phase, the recipient bed is routinely assessed by visual examination and palpation, as well as by periapical and panoramic radiology. These two imaging modalities provide a two-dimensional image of mesial-distal and occlusal-apical dimensions of the edentulous regions where implants might be placed. When adequate occlusal-apical bone height is available for endosteal implants, the buccal-lingual width and angulation of the available bone are the most important criteria for implant selection and success. However, neither buccal-lingual width nor angulation can be visualized on most traditional radiographs. Although clinical examination and traditional radiographs may be adequate for patients with wide residual ridges that exhibit sufficient bone crestal to the mandibular nerve and maxillary sinus, these methods do not allow for precise measurement of the buccolingual dimension of the bone or assessment of the location of unanticipated undercuts. For these concerns, it is necessary to view the recipient site in a plane perpendicular to a curved plane through the arch of the maxilla or mandible in the region of the proposed implants. Implant dentists soon recognized that, for optimum placement of implants, cross-sectional views of the maxilla and mandible were the ideal means of providing necessary pre-operative information. Today, the two most often employed and most applicable radiographic studies for implant treatment planning are the panoramic radiograph and tomography. Although distortion can be a major problem with panoramic radiographs, when performed properly they can provide valuable information, and are both readily accessible and cost efficient. To help localize potential implant sites and assist in obtaining accurate measurements, it is recommended that surgical stents be used with panoramic radiographs. In simple cases, where a limited number of implants are to be placed, panoramic radiography and/or tomography may be used to obtain a view of the arch of the jaw in the area of interest. For complex, cases, where multiple implants are required, the CT scan imaging procedure is recommended. Because of its ability to reconstruct a fully three dimensional model of the maxilla and mandible, CT provides a highly sophisticated format for precisely defining the jaw structure and locating critical anatomic structures. The use of CT scans in conjunction with software that renders immediate "treatment plans" using the most real and accurate information provides the most effective radiographic modality currently available for the evaluation of patients for oral implants. To follow patients after implant surgery, DSR can be helpful by addressing the limitations of other radiographic modalities in detecting postoperative changes. By eliminating unchanged information, DSR allows the clinician's eye to focus on actual changes that have occurred between the recordings of two images.

Cephalometry↗