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C Porta

Publications and source records attributed to C Porta.

At least 55 records · Page 3Linked to original sources
PubMed1999

Different kinds of polypeptides and polypeptide-coated nanoparticles are accepted by the selective transcytosis shown in the rabbit nasal mucosa.

The specific transcytosis of polypeptides, demonstrated in the nasal respiratory mucosa of the rabbit, seems to be involved in antigen sampling at the airway entry, since absorption has been shown only to occur if lymphoid aggregates are present beneath the epithelium and to be proportional to aggregate volume. Nanoparticles and many polypeptides besides the two previously tested (i.e. carbocalcitonin (CCT) and adrenocorticotropic hormone) should be transportable, in agreement with the vesicular transcytosis and antigen sampling hypothesis. Thus unidirectional mucosa-submucosa and opposite fluxes (Jms, Jsm) and the corresponding net fluxes (Jnet) of uncoated or polypeptide-coated polystyrene nanospheres (diameter: about 0.5 micrometer) have been measured with the aid of spectrophotometry and quantitative dark-field microscopy. No net transport has been observed for uncoated beads, whereas it has always been shown for polypeptide-coated beads, although to different extents. The selectivity sequence for the polypeptides tested is as follows: BSA congruent with enkephalin << anti-BSA IgG congruent with IgA congruent with CCT congruent with insulin </=anti-insulin IgG. With the exception of BSA and enkephalin-coated beads, whose Jnet is very small, in all the other cases the apparent affinities for receptors seem to be equal or similar; just over 6% polypeptide coating on the nanosphere is sufficient to elicit maximal transport; finally, transport seems to require many cooperating binding sites between the single nanosphere and receptors or one or many non-cooperating binding sites, but with a threshold number of polypeptide molecules adsorbed on the nanosphere to reach a minimal binding probability.

Adsorption↗
PubMed1999

Identification of particular epithelial areas and cells that transport polypeptide-coated nanoparticles in the nasal respiratory mucosa of the rabbit.

The active transcytosis of many different polypeptides (either presented free or adsorbed on latex nanoparticles), found in the respiratory mucosa of the upper nasal concha, has previously been shown to be proportional to the total volume of the lymphoid aggregates present in the tissue. By combining the use of fluorescent nanoparticles, flux measurements, confocal and scanning electron microscopy and conventional histology, it is shown in this paper that: (i) the areas of epithelium overlying lymphoid aggregates are the only transporting polypeptides; (ii) the respiratory epithelium in these areas consists mainly of non-ciliated microvillar cells, with numerous ciliated cells and rare mucous goblet cells at the periphery of the area only; (iii) non-ciliated microvillar cells are distinguishable in cells with well developed finger-like microvilli and cells with an irregularly pleated apical membrane, similar to that of intestinal and bronchial antigen-sampling M-cells; (iv) groups of polypeptide-coated nanospheres are found bound to this latter type of cells, demonstrating that these are the transporting cells, detected at the first stage of the transcytotic cycle.

Animals↗
PubMed1999

Position-dependent processing of peptides presented on the surface of cowpea mosaic virus.

The plant virus cowpea mosaic virus (CPMV) has been developed as an epitope-presentation system. Numerous epitopes have been expressed in the betaB-betaC loop of the CPMV small coat protein, all of which undergo a cleavage reaction between their two carboxy-terminal residues. Although many peptides presented in this manner give an authentic immune response, this was not the case for the NIm-1A epitope from human rhinovirus-14. Crystallography revealed significant differences between the structure of NIm-1A on CPMV compared with its native configuration. The 3D structure of C PMV expressing NIm-1A was used to design alterations to the context of the NIm-1A graft.

Amino Acid Sequence↗
PubMed1999

Circulating progenitor cell release and functional characterization after topotecan plus G-CSF and erythropoietin in small cell lung cancer patients.

Topotecan is a new antineoplastic agent active in ovarian cancer, with promising activity in small cell lung cancer and predictable toxicity. As a part of our ongoing attempt to optimize the use of disease-specific drugs as circulating progenitor cell (CPC) priming in solid tumors, we have evaluated the effects on CPC release of single-agent Topotecan followed by granulocyte colony-stimulating factor (G-CSF) + human recombinant erythropoietin (rhEPO), together with the cell cycle status of the collected CD34+ cells. Ten pretreated patients with small cell lung cancer received Topotecan (1 mg/m2, i.v. for 5 consecutive days) followed by G-CSF (5 microg/kg/day, s.c.) + rhEPO (10,000 I.U. daily, s.c.), starting 24 h after Topotecan. The combination was well tolerated and no relevant side-effects were recorded. On day +10 (range +9 to +11) after the last dose of Topotecan, the median WBC count and the CD34+ cell peak were 8.2 x 10(3) microl (range 4.9-13.9) and 55 microl (range 28-75), respectively. Using flow cytometry, a detailed cell cycle analysis was performed on these CD34+ cells. The cell cycle distribution was determined by DNA content coupled with bromodeoxyuridine incorporation analysis. Apoptosis was evaluated by quantitating DNA strand breaks. The percentage of CD34+ cells in active S-phase was 10.2+/-5%, while early apoptotic CD34+ cells were detected in a low percentage (5.5+/-3%). Topotecan followed by G-CSF + rhEPO mobilizes CPCs effectively. This sequence exerts a stimulation on CD34+ cell cycle with a protective effect from chemotherapy-induced apoptosis. Taken together, these data could be of value for the incorporation of Topotecan, as well as of the combination of G-CSF and rhEPO, into high-dose chemotherapy programs with CPC support.

Adult↗
PubMed1999

Cancer chemotherapy-related thrombotic thrombocytopenic purpura: biological evidence of increased nitric oxide production.

The occurrence of thrombotic thrombocytopenic purpura (TTP) in cancer patients receiving chemotherapy has been well established; although this entity is rare, its clinical importance seems to be growing. We describe 3 cases of TTP developing in cancer patients receiving different chemotherapeutic regimens. Using a sensitive high-performance liquid chromatographic method, we evaluated the stable nitric oxide end products, nitrite and nitrate, in the plasma of these patients. Nitric oxide is one of the key components involved in maintaining the normal nonthrombogenicity of the vascular endothelium. In our 3 patients, we found increased nitrate titers that were substantially higher than those observed in patients with de novo TTP. The observed increased release of nitrate could be interpreted as the consequence of massive disruption of endothelial integrity, with consequent passive nitric oxide release in vivo, or an adaptive mechanism of the endothelium to compensate for diffuse microvascular occlusion. The 2 mechanisms may both be involved, but the normal titers of nitric oxide end products in de novo TTP suggest that the former mechanism is more important, at least in cancer chemotherapy-related TTP.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Thrombotic thrombocytopenic purpura and autoimmunity: a tale of shadows and suspects.

BACKGROUND AND OBJECTIVE: The key pathogenic feature of TTP is the formation of platelet aggregates within the microcirculation; however, the etiology of such aggregates has been elusive for years. A large amount of evidence points to an abnormal interaction between damaged vascular endothelium and platelets, although the cause of the primary microvascular endothelial cell injury is seldom clear. The autoimmune hypothesis often recurs, and this is based on a number of observations: the claimed superiority of plasma-exchange over plasma infusion, the anecdotal report of the presence of immunocomplexes and autoantibodies in TTP patients, the efficacy of the administration of corticosteroids and other immunosuppressant agents, and the concomitant occurrence of TTP in association with autoimmune diseases, especially systemic lupus erythematosus (SLE). This review will focus on the complex relationships between TTP and humoral autoimmunity; in particular, similarities and differences between TTP, SLE and antiphospholipid (aPL) antibodies syndrome, as well as the putative role of several other antibodies directed towards endothelial cells and/or platelets, including the recently discovered anti-CD36 antibodies and antivWF-cleaving metalloprotease, will be discussed. DESIGN AND METHODS: The authors have been involved in the study and treatment of TTP and autoimmune diseases for years; furthermore, the PubMed data base of the National Library of Congress has been extensively searched using the Internet. CONCLUSIONS: Although over the years evidence has increased in favor of the autoimmune hypothesis for TTP etiopathogenesis, TTP should not yet be considered an autoimmune disease. Autoantibodies should be regarded as only one of the many different insults which can trigger microvascular thrombosis even though the autoimmune theory of the pathogenesis of TTP is gaining more and more strength. As far as concerns the relationship between TTP, SLE and aPL antibodies-related disorders, these diseases should be distinguished on the basis of both different clinical presentations and accurate antibody screening, although this approach should definitely not delay the prompt start of treatment.

ADAM Proteins↗
PubMed1999

Prospective, randomized trial of sequential interleukin-3 and granulocyte- or granulocyte-macrophage colony-stimulating factor after standard-dose chemotherapy in cancer patients.

BACKGROUND AND OBJECTIVE: Several in vitro and animal studies have shown that IL-3 primes hematopoietic stem cells to become more sensitive to later acting growth factors. We wanted to compare the toxicity and the synergistic stimulatory effect of interleukin-3 (IL-3) followed by granulocyte colony-stimulating factor (G-CFS) or granulocyte-macrophage colony-stimulating factor (GM-CSF) on white blood cell (WBC) and platelet counts, after standard-dose chemotherapy (CT) in patients with solid tumors. DESIGN AND METHODS: Fifty consecutive cancer patients with thrombocytopenia and/or leukopenia registered during a previous course of CT were randomized to receive, after the following course, IL-3 (10 microg/kg/day, s.c., day 1-5) followed by G- or GM-CSF (5 microg/kg/day, day 6-8). RESULTS: The nadir of WBC in the cycles supported with the combination of IL-3 and G-CSF was significantly higher than that observed in the CT cycles not supported by growth factors (p < 0. 005). Furthermore, severe leukopenia was abrogated in all the cycles supported with IL-3+G-CSF, while in the cycles without cytokines, this event was registered in 62.5% of the cases (p < 0.0005). Finally, the recovery of WBC was achieved a mean of 4 days earlier in the cycles supported with IL-3+G-CSF. As for thrombocytoprotection, no significant differences were evidenced, but severe thrombocytopenia was abrogated in all the cycles supported by IL-3+G-CSF (p < 0.05). Furthermore, platelet recovery after CT was achieved on average 3.5 days earlier in the IL-3+G-CSF group than in the previous cycles. The nadir of WBC count in the cycles supported by the combination of IL-3 and GM-CSF was significantly higher than that observed in the CT cycles not supported by growth factors (p < 0.005). Furthermore, severe leukopenia was abrogated in 40% of the cycles supported by IL-3+GM-CSF, while in the cycles without cytokines, this event was registered in 80% of the cases (p < 0.005). Finally, the recovery of WBC was achieved a mean of 3.5 days earlier in the cycles supported by IL-3+GM-CSF. As far as thrombocytoprotection is concerned, there were no significant differences in the nadir between the cycles supported by the association IL-3+GM-CSF and the cycles not supported by cytokines. However, severe thrombocytopenia was registered in 20% of the cycles not supported by growth factors but in only 10% of the cycles supported by IL-3+GM-CSF (p < 0.05). Furthermore, platelet recovery after CT was achieved on average 3 days earlier in the IL-3+GM-CSF group. The combination of IL-3 and G-CSF would appear to be more effective than the combination of IL-3 and GM-CSF in the control of both severe thrombocytopenia and leukopenia. Indeed, severe leukopenia was abrogated in all the cycles in arm A, but only in 40% of the cycles in arm B (p < 0.0005). Furthermore, considering a platelet count below 49

Adult↗
PubMed1999

Needlestick injuries among health care workers. A literature review.

Needlestick injuries among health care workers are a recognized health hazard, with 400,000 needlesticks occurring annually among the 4 million health care workers in the United States. Existing needlestick injury literature primarily focuses on hospital sites and may not be generalizable to other health care settings such as nursing homes, home health care sites, clinics, and emergency response units. Nurses were at high risk of needlestick injury from syringes and i.v. equipment relative to the other health care workers. Recapping, prohibited by the OSHA Bloodborne Pathogens Standard, continues to be an identified cause of injury. The literature supports comprehensive injury prevention and control strategies in conjunction with the use of safer needle devices. Health care organizations should assess their worksites to identify hazards and select products and strategies to correct the problem. Future research should clarify accurate needlestick injury rates (e.g., establish consistent denominators), address non-hospital setting risks, validate self reported data, and evaluate comprehensive interventions that employ engineering strategies to minimize the risk.

Accidents, Occupational↗
PubMed1998

Altered expression of heterogenous nuclear ribonucleoproteins and SR factors in human colon adenocarcinomas.

Alternative splicing is part of the expression program of a wide number of genes implicated in cell growth and differentiation. Although the occurrence of inappropriate alternative splicing in tumors has started to emerge, the underlying molecular mechanisms have been, thus far, largely unexplored. We have investigated the alternative splicing pattern of the CD44 gene in specimens of nonfamilial colon adenocarcinomas at different stages of tumor progression. In the same patients, we have assessed by Northern blotting analysis the mRNA levels of different heterogeneous nuclear ribonucleoproteins and SR factors, all involved in pre-mRNA splicing and, more in general, in mRNA maturation. The results of this analysis highlight a general rule for the mode of splicing of the CD44 pre-mRNA. Moreover, we found that the mRNA levels of different SR proteins in tumor specimens are different from, and usually lower than, those detected in samples of nonpathological tissue adjacent to the tumor. Quantitative analysis demonstrates that, in tumors, the mRNA levels of ASF, SRp40, SRp55, and SRp75, when normalized to those of heterogeneous nuclear ribonucleoprotein A1, are lower than those of SRp20 and SRp30. Interestingly, this reduction is more drastic in patients showing a more altered CD44 splicing pattern and seems to be related to the propensity to develop metastases.

Adenocarcinoma↗
PubMed1998

Nitrite/nitrate balance during photoinduced cerebral ischemia in the rat determined by high-performance liquid chromatography with UV and electrochemical detection.

A specific and simple method for the direct simultaneous detection of extracellular nitrite (NO2-) and nitrate (NO3-) has been developed, using high-performance liquid chromatography separation with UV and electrochemical detection in series. These stable endproducts of nitric oxide (NO.) were determined in dialysis perfusate obtained through in vivo brain microdialysis during and after experimental photoinduced cerebral ischemia in rats. The chromatographic conditions were optimized with a reversed-phase column (250 x 46 mm) using 10 mM n-octylamine pH 6.0 as a mobile phase. Absorbance was measured at 220 nm for NO3- detection; electrochemical detection was performed at +0.7 V for NO2- evaluation. This assay system holds the advantages of in vivo consecutive measurements, high precision, good reproducibility, technical simplicity, fast response (about 7 min), and wide availability.

Animals↗
PubMed1998

Relationship between polypeptide transcytosis and lymphoid tissue in the rabbit nasal mucosa.

It has been suggested that the specific transcytosis of polypeptides, demonstrated in rabbit nasal mucosa (upper concha), is involved in antigen sampling at the airway entry. To test this hypothesis, unidirectional transepithelial fluxes of carbocalcitonin (CCT Mw = 3362) from the mucosal to the submucosal side, and vice versa, were measured by radioimmunoassay every 30 min for 120 min and, from the difference, net absorption was determined in the upper concha and septum mucosae. The exposed mucosae were examined by quantitative histology; isolated scattered lymphoid cells/mm2 and volumes of lymphoid infiltrates and aggregates were quantified. CCT absorption was observed in the mucosae of the upper concha and septum provided that aggregates were present, being proportional to aggregate volume. No relationship was noted with isolated scattered lymphoid cells and infiltrates. Passive permeability was unaffected by lymphoid tissue. On this basis, the antigen sampling hypothesis seems to be at least partially substantiated.

Animals↗
PubMed1998

Scope for using plant viruses to present epitopes from animal pathogens.

Epitope presentation to the immune system for vaccination purposes can be achieved either via an inactivated or attenuated form of a pathogen or via its isolated antigenic sequences. When free, these peptides can adopt a variety of conformations, most of which will not exist in their native environment. Conjugation to carrier proteins restricts mobility of the peptides and increases their immunogenicity. A high local concentration of epitopes boosts the immune response further and can be generated by the use of self-aggregating carriers, such as the capsid proteins of viruses. In this regard plant viruses have in recent years started to make an impact as safer alternatives to the use of bacterial and attenuated animal viruses: the latter both require propagation in costly cell-culture systems where they can undergo reversion towards a virulent form and/or become contaminated by other pathogens. Plant virus-based vectors can be multiplied cheaply and to high yields (exceeding 1 mg/g plant tissue) in host plants. Both helical (tobacco mosaic virus, potato virus X, alfalfa mosaic virus) and icosahedral (cowpea mosaic virus, tomato bushy stunt virus) particles have been used to express a number of animal B-cell epitopes, whose immunogenic properties have been explored to varying degrees. Copyright 1998 John Wiley & Sons, Ltd.

Journal Article↗
PubMed1998

Endothelin-1 and 5-fluorouracil-induced cardiotoxicity.

Cardiotoxicity is an uncommon side-effect of 5-FU-based chemotherapy. Coronary artery vasospasms have been postulated to be involved in the pathogenesis of this rare but serious problem. We found high plasma levels of ET-1, a potent natural vasoconstrictor, in two patients who experienced two of the commonest clinical manifestations of 5-FU-induced cardiac toxicity--i.e., angina pectoris and chronic heart failure. We, therefore, propose ET-1 as the ultimate mediator of this toxicity, even though the mechanism of ET-1 increase in peripheral venous blood is still unknown. Finally, another important question still remains unresolved: is the release of ET-1 from normal coronary endothelial cells the prime cause or simply the consequence of 5-FU-related cardiotoxicity?

Aged↗