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Biomedical subjects

C Porta

Publications and source records attributed to C Porta.

At least 73 records · Page 4Linked to original sources
PubMed1998

Platelet agonists and calcium homeostasis in endothelial cells: possible role in the interaction of endothelium with hemostatic system.

BACKGROUND AND OBJECTIVE: The endothelium is complex tissue that modulates a vast array of biological functions and Ca++ transients are critically important to these endothelium-dependant functions. We addressed the hypothesis that some platelet agonists and products of activation of the hemostatic system could determine Ca++ transients in a bovine pulmonary artery endothelial cell line (CPA-47). DESIGN AND METHODS: The effect of thrombin, collagen, ADP, PAF, PDGF, GRGDS, and the TxA2 mimetic U46619 on CPA-47-cytoplasmic Ca++ transients was evaluated using a Platelet ionized Calcium Aggregometer, after cells were loaded with the photoprotein aequorin. RESULTS: ADP, GRGDS, PAF, U46619 and collagen were able to induce rapid Ca++ transients in CPA-47 endothelial cells and the response was stable after repeated additions, while thrombin acted slightly differently, as cells became refractory to this agonist after the first response, but they remained sensitive to the other inducers. Only PDGF was completely ineffective. Furthermore, calcium-channel blockers verapamil and flunarizine (but not nifedipine) caused a reduction only of thrombin-induced cytoplasmic Ca++ transients, while the addition of depolarizing concentration of KCl suggests the presence also of voltage-operated channels on endothelial cell membrane. Finally, EGTA caused the complete suppression of Ca++ transients induced by all the tested agonists but collagen. INTERPRETATION AND CONCLUSIONS: Our study demonstrated that the different agents tested are able to induce Ca++ transients on bovine endothelial cultured cells, similarly to that observed in platelets and other non excitable cells, including tumor cells, and that calcium channel blockers had only a limited inhibitory effect on these changes; these results may help more thorough understanding of the biochemical basis of the interaction between endothelium and the hemostatic system.

Animals↗
PubMed1998

Atrial septal aneurysm in a patient with pseudoxanthoma elasticum.

Pseudoxanthoma elasticum (PXE) is a rare heritable disorder of the connective tissue characterized by marked clinical heterogeneity. Common cardiovascular complications of PXE include renovascular hypertension, premature coronary artery disease and calcification of peripheral arteries frequently leading to claudicatio intermittens; fibrous thickening of the endocardium and atrioventricular valves, leading to restrictive cardiomyopathy and/or mitral valve prolapse have been also described. We herein report on a PXE patient who developed an atrial septal aneurysm as a previously undescribed cardiologic manifestation of her disease.

Adult↗
PubMed1997

Epirubicin and etoposide combination chemotherapy to treat hepatocellular carcinoma patients: a phase II study.

Approximately half the patients affected with hepatocellular carcinoma (HCC) present with unresectable disease, so that efficacious systemic chemotherapy protocols are badly needed. We report the results of a phase-II study aimed at testing the efficacy and toxicity of a combination of epirubicin and VP-16. Thirty six patients (80 men and 6 women) received epirubicin (40 mg/m2, on day 1) and VP-16 (120 mg/m2, on days 1, 3 and 5) every 28th day. Chemotherapy was stopped in case of disease progression, while the patients who achieved an objective response or who had stable disease continued treatment for a maximum of 10 cycles. One patient (3%) achieved a complete response, while 13 patients (36%) achieved partial response, i.e. 14 objective responses in all (39%, 95% CI: 23-55%). 11 patients (31%) exhibited stable disease, while in the other 11 patients (31%) the disease progressed. Median overall survival time was 10 months and 13.5 months in the subgroup of patients responding to treatment. Significant, especially haematological, toxicity was documented, but in no case was it so severe as to require discontinuation of treatment or reduction of the dosage. In conclusion, this combination appears to be an active and tolerable therapeutic option for HCC patients who are not candidates for surgical or locoregional procedures, and in our opinion it deserves further exploration within a randomised controlled trial versus best supportive therapy.

Aged↗
PubMed1997

Plant-derived vaccine protects target animals against a viral disease.

The successful expression of animal or human virus epitopes on the surface of plant viruses has recently been demonstrated. These chimeric virus particles (CVPs) could represent a cost-effective and safe alternative to conventional animal cell-based vaccines. We report the insertion of oligonucleotides coding for a short linear epitope from the VP2 capsid protein of mink enteritis virus (MEV) into an infectious cDNA clone of cowpea mosaic virus and the successful expression of the epitope on the surface of CVPs when propagated in the black-eyed bean, Vigna unguiculata. The efficacy of the CVPs was established by the demonstration that one subcutaneous injection of 1 mg of the CVPs in mink conferred protection against clinical disease and virtually abolished shedding of virus after challenge with virulent MEV, demonstrating the potential utility of plant CVPs as the basis for vaccine development. The epitope used occurs in three different virus species-MEV, canine parvovirus, and feline panleukopenia virus- and thus the same vaccine could be used in three economically important viral hosts-mink, dogs, and cats, respectively.

Amino Acid Sequence↗
PubMed1997

[Postpartum myoglobin blood monitoring in newborns. Correlations with renal function in the first 48 hours of life].

BACKGROUND: Myoglobin is a muscular tissue protein, and it is a very early damage index. As the newborn "thin mass" is less than that of the adult and knowing the renal dynamics of this protein clearance, the authors have analyzed the correlation between myoglobinemia and transitory renal failure, which is frequently present in newborns with fetal distress. METHODS: We examined a random population of 56 newborns (33 eutocic deliveries 14 caeserotomy, 9 various degrees of fetal distress) to which, after having had the parents' informed consent, the microsamples pattern was fixed at 0, 6, 12, 24, 48 hours from birth at the same time of ordinary exams to gauge: myoglobin with nephelometric method, CPK, creatininemia, azotemia and transaminase. The same exams were camed out on the mother at the beginning of labor and after delivery. RESULTS: We found that the placenta is not permeable to mother myoglobin, at the sixth hour from birth we have the highest value, while CPK is lower to increase, myoglobinemia associated with myoglobin variations. CONCLUSIONS: Myoglobinemia might be monitored to prevent distressed newborns from transitory renal tubular defect, justifying forced diuresis and urinary alkalosis.

Humans↗
PubMed1996

The active transport of polypeptides in the rabbit nasal mucosa is supported by a specific vesicular transport inhibited by cytochalasin D.

We have previously demonstrated that polypeptides (elcatonin and ACTH) can be actively absorbed across the rabbit nasal mucosa. In this paper we show that elcatonin is also transported when it is adsorbed onto microspheres (diameter: 0.5 micron). whereas the elcatonin-uncovered microspheres do not display any net transport. Cytochalasin D (0.1 microgram/ml) abolishes the net absorption of elcatonin presented either alone or adsorbed. At the same concentration the inhibitor does not affect cellular active ion transports (and hence metabolism); although it increases intercellular ion and elcatonin permeability, it does not affect intercellular and paracellular permeability of the elcatonin-covered microspheres. Altogether, these results show that polypeptide transport is supported by a specific vesicular transfer inhibited by cytochalasin D by disassembly of the actin cytoskeleton, probably at the apical border of the cell.

Absorption↗
PubMed1996

Endocytosis inhibitors abolish the active transport of polypeptides in the mucosa of the nasal upper concha of the rabbit.

An active absorption of polypeptides (elcatonin = CCT; adrenocorticotropic hormone) had been previously observed in the nasal respiratory mucosa of the rabbit. Its saturation kinetics and the parallel absence of a net transfer of other non-polypeptidic organic markers excluded the involvement of a simple pinocytosis. This absorption has been now better localized and further characterized. Unidirectional CCT fluxes (determined with radioimmunoassay) have been concomitantly monitored with transepithelial electric potential difference (Vms). Although the mucosae covering the ectoturbinal A and the lower and upper conchae displayed similar Vms, the active CCT transport was only evidenced in the upper concha. In this region cytochalasin B (which by disassembling actin microfilaments prevents the apical formation of vesicles in epithelial cells) and monensin (which prevents the split of the ligand-receptor complex in the endosomes) both eliminated the net CCT absorption, however, also permanently increasing the passive CCT junctional permeability. Aluminum fluoride (which prevents the fusion of endocytic vesicles into endosomes) and colchicine (which disrupts microtubules along which vesicles move in the cytoplasm) also permanently abolished net CCT transport, without affecting, or shortly and transiently affecting, passive permeability. On the whole these results are in favor of an active CCT transport supported by a specific vesicular transport.

Aluminum Compounds↗
PubMed1996

Thrombotic thrombocytopenic purpura and relapses: why do case series differ? The Italian Cooperative Group for TTP.

We examined the retrospective case series of the Italian Cooperative Group to determine the incidence of relapses in TTP patients. Of 60 patients who have crossed the 10-year threshold from the first episode, only 9 (15%) relapsed during that period, a figure far lower than that reported recently. Such difference is hardly explainable on the basis of our current knowledge of the biological behaviour of TTP. Furthermore, we unsuccessfully analyzed the treatment performed in each of our relapsed patients, in search of some element that could retrospectively predict the subsequent relapse.

Adult↗
PubMed1996

Use of viral replicons for the expression of genes in plants.

Autonomously replicating virus-based vectors have been investigated as a means of introducing heterologous genes into plants. This approach has a number of potential advantages over stable genetic transformation, particularly in terms of speed and levels of expression that can be obtained. Several groups of plant viruses, with genomes consisting of both DNA and RNA, have been investigated as possible gene vectors. In the case of DNA viruses, it has generally been possible to identify nonessential regions of the genome that can be replaced by foreign sequences. However, there appear to be limitations on the size of insert which can be tolerated. In the case of RNA viruses, replacement of viral sequences usually has a drastic effect on the viability. However, in several cases it has proved possible to substantially increase the size of the viral genome by the direct insertion of additional sequences while still retaining the ability of the viruses to multiply and spread in plants. These RNA virus-based systems appear to have the greatest potential as gene vectors.

Capsid↗
PubMed1996

5-methyltetrahydrofolate or 5-formyltetrahydrofolic acid to modulate 5-fluorouracil's cytotoxic activity in vivo. A phase II study in patients with advanced colon cancer.

The purpose of this study was to test the hypothesis that 5-methyltetrahydrofolate (Me-THF), a source of reduced folates alternative to leucovorin, could effectively modulate 5-fluorouracil's (5-FU) cytotoxic activity in patients with advanced colon cancer. A total of 23 patients were enrolled in a phase 11 trial; they received 5-FU as a 30-min infusion at a dose of 370 mg/m2 following a rapid i.v. push of 200 mg/m2 Me-THF, both drugs being given for 5 consecutive days. Cycles were repeated every 4 weeks until disease progression. No patient achieved a complete response. In all, 4 patients showed a partial response (17.4%), 7 developed stable disease (30.4%), and the remaining 12 (52.2%) progressed. Toxicity was acceptable and never exceeded WHO grade III intensity. According to our experience, the MeTHF/5-FU combination does not appear to be an effective treatment for advanced colon cancer. Despite its low toxic profile, in our opinion its wider use should be discouraged.

Adult↗
PubMed1996

Stimulation of neutralizing antibodies to human immunodeficiency virus type 1 in three strains of mice immunized with a 22 amino acid peptide of gp41 expressed on the surface of a plant virus.

A plant virus, cowpea mosaic virus, expressing a 22 amino acid peptide 731-752 of the gp41 glycoprotein of human immunodeficency virus type 1 (HIV-1 IIIB), was shown previously to stimulate HIV-1 cross reactive neutralizing antibodies in adult C57/BL6 mice. Here some parameters concerning the stimulation of HIV-1-specific neutralizing and ELISA antibody have been determined in adult C57/BL6, C3H/He-mg and BALB/c mice. Two injections per mouse of all CPMV-HIV/1 doses tested (100, 10 and 1 microgram chimera which contained, respectively, 1700, 170 and 17 ng HIV peptide per injection) stimulated a strong serum neutralizing antibody response in all mice. One hundred micrograms or 10 micrograms CPMV-HIV/1 per injection gave 99% neutralization of HIV-1 IIIB in C8166 cells at a serum dilution of 1/200, whereas sera from mice immunized with 1 microgram per injection neutralized virus to 97%, 79% and 63% at a 1/200 dilution of serum from C3H/He-mg, C57/BL6 and BALB/c mice, respectively. Restimulation of these mice with the same immunogen dose marginally increased the neutralization titres. The longevity of the neutralizing antibody response increased as the immunogen dose decreased, and was dependent on the strain of mouse, in the order C57/BL6C3H/He-mg BALB/c. Re-immunization with a third injection improved the longevity of the antibody response. All mice immunized with 100 micrograms CPMV-HIV/1 responded with ELISA antibody to the gp41 peptide bound in solid phase. Ten micrograms stimulated ELISA antibody in some but not all mice, while mice immunized with 1 microgram had no detectable ELISA antibody. This synthesis of ELISA antibody decreased > or = 230-fold over the range of immunogen doses tested but, in the same mice, the neutralizing antibody response decreased only twofold, showing an unusual bias to production of the latter. Neutralizing antibodies were thus stimulated at a lower immunogen dose than ELISA antibodies. Antibody which was affinity purified using the free gp41 peptide gave a good ELISA titre but did not neutralize HIV-1, suggesting that the neutralizing antibody is recognizing a conformational epitope on the gp41 oligomer.

Amino Acid Sequence↗
PubMed1996

Structure-based design of peptide presentation on a viral surface: the crystal structure of a plant/animal virus chimera at 2.8 A resolution.

BACKGROUND: We employed a genetically engineered icosahedral plant virus, cowpea mosaic virus (CPMV), as an expression and presentation system to display a 14 amino acid linear antigenic epitope found in a capsid protein of human rhinovirus 14 (HRV14). RESULT: Gram quantities of the CPMV/HRV 14 chimera were made in plants and purified particles were crystallized in a form isomorphous with wild-type CPMV. The 2.8 A resolution structure of the chimera shows that the inserted loop is well ordered and that if the loop were intact, a phenylalanine residue of CPMV would be placed in a hydrophilic environment. The resultant strain may make the loop an attractive substrate for endogenous plant proteases, as roughly 80% of the inserted polypeptides are cleaved, allowing the phenylalanine to be partially buried. Altering the phenylalanine to an arginine could relieve the stress, reducing the propensity for cleavage and increasing the likelihood that the peptide will assume a structure closely similar to its structure in HRV14. CONCLUSIONS: Successful crystallization of other CPMV chimeras in forms isomorphous with the native virus suggests that this is a viable system for structure-based design of peptide presentation.

Amino Acid Sequence↗
PubMed1996

Inhaled sodium cromoglycate to treat cough in advanced lung cancer patients.

C-fibres probably represent the common final pathway in both ACE inhibitors and neoplastic cough. A recent report demonstrated that inhaled sodium cromoglycate is an effective treatment for ACE inhibitors' cough; this effect might be due to the suppression of afferent unmyelinated C-fibres. We tested the hypothesis that inhaled sodium cromoglycate might also be effective in lung cancer patients who presented with irritative neoplastic cough. Twenty non-small-cell lung cancer (NSCLC) patients complaining of cough resistant to conventional treatment were randomised to receive, in a double-blind trial, either inhaled sodium cromoglycate or placebo. Patients recorded cough severity daily, before and during treatment, on a 0 to 4 scale. The efficacy of treatment was tested with the Mann-Whitney U-test for non-parametric measures, comparing the intergroup differences in the measures of summary of symptom scores calculated in each patient before and after treatment. We report that inhaled sodium cromoglycate can reduce cough, also in NSCLC patients and that such reduction, observed in all patients treated, is statistically significant (P < 0.001). Inhaled sodium cromoglycate appears to be a cost-effective and safe treatment for lung cancer-related cough.

Administration, Inhalation↗