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Biomedical subjects

F Esposito

Publications and source records attributed to F Esposito.

At least 91 records · Page 5Linked to original sources

Comparison of the number of IL-4 and IFN-gamma secreting cells in response to the malaria vaccine candidate antigen Pf155/RESA in two groups of naturally primed individuals living in a malaria endemic area in Burkina Faso.

The enzyme-linked immunospot (ELISPOT) assay was used to enumerate the number of IFN-gamma and IL-4 producing cells after in vitro stimulation with a highly purified recombinant malaria vaccine candidate antigen (r-Pf155/RESA) or synthetic peptides corresponding to its major T-cell epitopes. Two groups of naturally primed individuals living in rural areas of Burkina Faso were studied. The donors comprised one group of healthy (non-parasitemic) mainly adult people and one parasitemic mainly younger people. IL-4 producing cells were detected in response to PHA but no such cells were detected in response to the malarial antigens. The most frequent IFN-gamma responses were seen with r-Pf155/RESA. Thus, after stimulation with this antigen 52% of the donors responded positively in the ELISPOT assay, while only 17% responded to the synthetic peptides, suggesting that the rPf155/RESA contained T-cell epitopes not covered by the peptides used in this study. The number of IFN-gamma producing cells in response to the malarial antigens did not differ between the two groups. However, IFN-gamma levels found in sera from the parasitemic individuals were significantly higher than in those from healthy donors. This latter finding and the lack of differences seen in the number of IFN-gamma producing spots in the two groups indicate that IFN-gamma producing cells may have sequestered to other organs in the parasitemic group.

Adolescent↗

[Association of Morris' syndrome with squamous cell carcinoma of the vulva].

We described a case of squamous cell carcinoma of the vulva in a patient with Morris' syndrome. In these patients, there is an increased risk of gonadal neoplasms. On the contrary, neoplasms originating from the vulvo-vaginal tract are very rare. Neoplasms arising from the neovagina have been reported. Therefore, a continued periodic surveillance of the external genitalia and the vagina is indicated.

Androgen-Insensitivity Syndrome↗

Plasmodium falciparum malaria in sympatric ethnic groups of Burkina Faso, west Africa.

Plasmodium falciparum parasite rate, parasite density and anti-CS antibodies were assessed in 196 subjects (age > 10 yrs) belonging to three sympatric West African ethnic groups, namely Mossi, Rimaibé and Fulani, all exposed to very high seasonal malaria transmission in the same rural village near Ouagadougou, Burkina Faso. No interethnic differences were noted in the use of antimalaria measures nor in the exposure to malaria vectors. However, interethnic differences were found in each of the three malariological indices. The Fulani appeared markedly less parasitized and more responsive to the CS-antigen than the Mossi and the Rimaibé who had very similar indices, except in the case of parasite density. These findings suggest a higher resistance to malaria of the Fulani ethnic group, possibly involving human genetic factors and/or the influence of extrinsic variables (e.g., socio-cultural) among which diet differences should be considered.

Adolescent↗

Inhibition of the differentiation of human myeloid cell lines by redox changes induced through glutathione depletion.

We have investigated the effect of redox changes in vivo on the differentiation of two human myeloid cell lines, HL-60 and KG-1. The glutathione-depleting agent diethyl maleate (DEM) prevented the development of differentiated features in response to phorbol esters, including adherence of the cells to plastic surfaces and repression of the myeloperoxidase and CD34 genes. Moreover, DEM abolished phorbol 12-myristate 13-acetate-induced activation of the transcription factors AP-1 and Egr-1, suggesting that inhibition of differentiation may be due, at least in part, to redox modifications of these proteins.

Antigens, CD↗

Clinical and tomographic findings in vascular dementia.

Vascular dementia (VD) may arise as a sequel to any form of cerebrovascular disease. Since only some patients with cerebrovascular disease will eventually develop dementia, we studied the morphological and clinical findings associated with dementia in cerebrovascular patients. The relationship between these factors and the dementia syndrome was evaluated in 25 patients with VD, and 68 non demented subjects with a history of cerebral ischemic attacks. We found that VD was significantly associated with white matter lesions and atrophy on CT-scan, and a high prevalence of frontal lobe symptoms and signs.

Aged↗

Effect of acclimatization to high altitude (5,050 m) on motor unit activation pattern and muscle performance.

This study evaluated the influence of acute and chronic hypoxia (up to 40 days at 5,050 m) on the muscle strength, fast-to-slow fiber motor unit (MU) ratio, and MU activation strategy. These factors were studied by measuring the maximal voluntary contraction (MVC) of the elbow flexors and analyzing surface electromyogram (EMG) and soundmyogram (SMG) of the isometrically contracting biceps brachii. From the time and frequency domain analysis of EMG and SMG, the root mean square and mean frequency of the spectra were calculated. SMG and EMG were recorded during 4-s exercises in the 20-100% MVC range before departure; after 2, 15, and 40 days at high altitude; and after the return to sea level. MVC or root mean square and mean frequency at all levels of effort were not significantly different among all experimental conditions. In the present study where optimal living conditions (i.e., food, physical activity, and environmental temperature) were ensured, acute and chronic hypoxia (at least up to 40 days) did not affect the maximal force output or fast-to-slow fiber MU ratio and MU activation pattern during isometric exercise.

Acclimatization↗

Short-term results of bovine internal mammary artery use in cardiovascular surgery.

Over a 14-month period, 28 bovine internal mammary arteries (Bioflow, Bio-Vascular, Inc.; St. Paul, Minnesota, USA) were implanted in 20 patients at our institutions. In 8 patients, the bovine internal mammary artery was used to bypass coronary vessels: in 4 of these patients, coronary artery bypass grafting was performed because of coronary disease (1 type-I aortic dissection); in the other 4 (all with aortic dissection), the modified Bentall technique was used for coronary artery reimplantation. In the remaining 12 patients, the bovine artery was used in vascular surgery: as a graft for lower-extremity occlusive disease (4 patients), arteriovenous fistula (2 patients), and aorticorenal bypass (1 patient); and as a patch to the carotid bifurcation or the common femoral artery in association with endarterectomy (5 patients). The 21 bovine grafts were all 5 mm in diameter; the 7 bovine patches were 4 mm. Of the 8 coronary bypass patients, 2 who underwent coronary artery bypass grafting had acute postoperative myocardial infarctions, and 2 who underwent the modified Bentall technique died in surgery. Follow-up angiography showed complete bovine internal mammary artery graft occlusion in 2 patients; 2 symptom-free patients refused examination. Of the vascular surgery patients, 1 with mild left leg claudication had graft occlusion, shown by angiography, 4 months after surgery. Renal scintigraphy performed in the patient with aorticorenal bypass 4 months after operation showed no blood flow to the kidney. Two patients died for reasons unrelated to bovine mammary artery grafting. The remaining patients are well and free of complications. In view of the high incidence of early occlusion, we do not recommend use of the bovine internal mammary artery graft in coronary surgery. In vascular surgery, the results are more encouraging; however, studies comprising a larger number of patients and longer follow-up are needed to determine whether the use of the bovine internal mammary artery graft can be recommended.

Adult↗

Isolation and structural characterization of the rat gene encoding the brain specific snRNP-associated polypeptide "N".

We isolated the gene encoding the brain specific snRNP-associated polypeptide "N" from a rat genomic library. Some intronless genes have previously been reported for this polypeptide in the rat. In contrast, our gene consists of at least nine exons (the last exon(s) encoding the 3'-end of the mRNA has not been isolated). The second intron of the gene is probably so long as to hamper the cloning of the complete gene into a single phage vector. Therefore, we used polymerase chain reaction amplification of the rat genome with oligonucleotides designed on the basis of known cDNA sequences that allowed us to isolate and clone the first two exons at the 5'-end of the gene. Primer extension studies revealed multiple transcription start sites, all of them contained within the first exon. The intron/exon organization coincides with the alternative splicing events suggested by the sequences of the various cDNA species isolated so far. As also reported by others, genomic Southern analysis suggests the presence of other genomic regions containing sequences strongly hybridizing to the cDNA. We isolated and characterized two of these regions. They contain sequences very similar to the cDNA, not interrupted by introns and flanked by a polyA tail at their 3'-ends; hence they are considered two different pseudogenes.

Amino Acid Sequence↗

Identification of a linear neutralization site within the third variable region of the feline immunodeficiency virus envelope.

Synthetic peptides have been used to map linear B-cell epitopes of the third variable (V3) region of the feline immunodeficiency virus (FIV) external membrane glycoprotein gp120. The analysis of sera from naturally and experimentally FIV-infected cats by Pepscan and enzyme immunoassay with four partially overlapping peptides evidenced three antibody-binding domains, two of which mapped in the carboxyl-terminal half of V3. In particular, the V3.3 sequence (Gly-392-Phe-413) turned out to be important for in vitro neutralization of the virus in that the peptide inhibited the FIV-neutralizing activity of pooled immune cat sera, and on the other hand, cat sera raised against this peptide effectively neutralized FIV infectivity for Crandell feline kidney cells.

Amino Acid Sequence↗

Structural pattern of the mitoses and hollow formations in the human embryo.

Hollow formations in very early stages of the human embryo development have been studied, regarding the behaviour of the mitoses. Semithin sections of the neural tube, of the fissure of the optic cup, and of somites yet furnished with the myocoelic cavity have been observed at the light microscope, after staining with toluidine blue. In all the observed buds a particular and very interesting result has been obtained: all the mitoses are placed in the lining cellular layer looking at the cavity. Dividing cells in the thickness of the wall of the buds are always lacking. In all the cases the dividing cells and the most of the others during the interphase appear to be closely linked to the inner surface of the wall, in the adluminal layer, at level of which cell evaginations form characteristic palings. A hypothesis has been advanced concerning the influence that active substances in the fluid filling the cavities may have in the control of the mitotic processes of the cellular wall.

Embryo, Mammalian↗

In vitro immune recognition of synthetic peptides from the Plasmodium falciparum CS protein by individuals naturally exposed to different sporozoite challenge.

The impact of duration and intensity of sporozoite challenge on the in vitro cell immune response to synthetic peptides of the circumsporozoite (CS) protein of Plasmodium falciparum was investigated in residents of a malaria endemic area in Burkina Faso (West Africa). Lymphocyte proliferation and interferon-gamma (IFN-gamma) production were used to assess immune recognition of synthetic peptides corresponding to the polymorphic Th2R and Th3R regions, to the conserved CS.T3 sequence and to NANP and degenerate NVDP repeats. Immune responses were measured in adults and children from a village where they received more than 100 sporozoite inoculations per year and in adults living in a town, exposed to a 10-100 times lower challenge. A lifetime intense exposure apparently increased the ability to proliferate in response to most peptides in the rural adults, who all produced antibodies to NANP repeats. Surprisingly, cell cultures from these subjects seldom contained appreciable levels of IFN-gamma. In the urban adults, possibly due to the moderate challenge they are exposed to, significant differences in the proliferative potentials of the peptides could be detected. The highest stimulation indices were obtained with the genetically unrestricted CS.T3 peptide. Remarkably, proliferative responses to Th2R and Th3R appeared to be correlated with the humoral response to the CS protein, indicating a T helper significance of the epitopes. The differing proliferative potential of the polymorphic epitopes in the urban adults suggests that polymorphism might delay the development of immune responsiveness under conditions of sporadic transmission. The children from the highly malarious village displayed the lowest proliferative scores, accompanied by a high prevalence of antibodies to NANP repeats. On the basis of these findings, the hypothesis is proposed that a pure B cell reactivity to NANP repeats could ontogenetically precede the mounting of a conventional T-B cooperative immune response.

Adult↗

Multiple antigen peptides for specific detection of antibodies to a malaria antigen in human sera.

Multiple antigen peptides (MAP), consisting of a number of peptide copies synthesized on a branching lysyl core, offer a novel approach for rendering small peptides immunoreactive in solid-phase immunoassays. An octameric MAP, carrying 6 repeats of the sequence -N-A-A-G-, tandem repeated in the immunodominant region of the circumsporozoite (CS) protein of Plasmodium malariae, was used as a model to evaluate the suitability of the MAP system in an indirect enzyme-linked immunosorbent assay (ELISA) for detecting antibodies against a parasite antigen in individuals exposed to natural infection. The reaction of endemic sera in ELISA on MAP8-(NAAG)6 was related to that obtained in immunofluorescence on sporozoites, indicating the specificity of the antibody-MAP interaction. The reactivity of immune sera was found to be directed only against the (NAAG)6 moiety of the MAP and not against the lysyl core, since antibody binding to MAP8-(NAAG)6 was completely inhibited by (NAAG)6-NA monomer, but remained uninfluenced when lysyl core was used as competing ligand. The levels of antibodies to MAP8-(NAAG)6, in two groups of individuals naturally exposed to malaria infection, appeared to be related to their respective exposure to the parasite.

Amino Acid Sequence↗

Morphological changes in human chorionic villi cultivated in conditioned atmospheres of gases.

With the aim to verify the changes that a reduction of the oxygen rate may elicit in the morphological pattern of the human chorionic villi, a new experimental procedure has been suggested. Chorionic villi from human early placentas were incubated in Dulbecco's modified medium of Eagle in the presence of oxygen, air or CO2 at a gas pressure equal to 0.7 atm. The specimens were fixed, dehydrated and embedded in resin, and semithin sections were obtained. Using an image analyser, the thickness of the trophoblastic layer and the mean radius of the villi were evaluated and the results submitted to a statistical analysis. The results show a decrease in the ratio thickness of the trophoblast/mean radius of the villus, directly proportional to the reduction of the oxygen percentage in the employed gases. The interesting conclusions demonstrate that the changes which affect the chorionic villi occur very early and are easily evaluable with quantitative methods; a clinical interest in the use of the proposed quantitative procedure can be emphasized.

Air↗

Waiting for the vaccine: sporozoite vaccine research entails important progress in malaria epidemiology.

The research efforts aimed at developing a vaccine against malaria, although failing thus far in their main objective, have produced molecular tools of great utility for epidemiological studies. For example, monoclonal antibodies directed against the repeats of Plasmodium circumsporozoite (CS) protein allowed the 2-site assay for detecting sporozoites in mosquitoes to be established. This immunoassay is advantageous compared with the conventional method of salivary gland dissection and microscopic examination, for it makes the identification of the sporozoite species possible, thanks to species-specific aminoacid sequences of the CS repeats. Other examples of vaccine research-derived tools are synthetic peptides reproducing the repetitive part of the CS protein, which allow antibodies to sporozoites, in individuals exposed to malaria, to be detected. Antibodies to the CS repeats of Plasmodium (Laverania) falciparum proved to be a reliable indicator of the intensity of malaria transmission and, therefore, were suitable for monitoring the impact of malaria control programmes. Finally, a project is outlined that, relying on the application of these tools, will aim at characterizing the transmission of Plasmodium (Plasmodium) malariae and at unveiling the possible relationship among different species thriving in the same distribution area, an issue which may become of relevance in view of the likely introduction of a vaccine directed against a single species.

Animals↗

Evaluation of an ELISA kit for epidemiological detection of antibodies to Plasmodium falciparum sporozoites in human sera and bloodspot eluates.

Antibodies to Plasmodium falciparum sporozoites represent a serological transmission indicator, which can be applied in epidemiological studies to estimate the intensity of malaria transmission. An ELISA method has been developed as an industrial kit to detect these antibodies, using a chemically synthesized (NANP)40 peptide as antigen. The results obtained with this kit are compared in the present paper with those obtained by an ELISA test already applied in epidemiological studies. In testing sera from individuals living in endemic areas, a high diagnostic concordance (92.1%) was obtained between the two assays. The absorbances of these sera correlated well, as shown by a correlation coefficient r = 0.877. Sera from individuals never exposed to malaria gave very low absorbances with the kit. This minimum non-specific binding increases the probability of comparable results in different studies. When the two ELISAs were evaluated for analytical sensitivity and precision, similar satisfactory results were achieved. The test can be performed not only with sera but also with eluates from filterpaper bloodspots. Modifications of the kit to reduce its cost and suggestions regarding distribution and funding are also proposed.

Animals↗

Intraerythrocytic administration of a synthetic Plasmodium antigen elicits antibody response in mice, without carrier molecules or adjuvants.

The synthetic peptide (NANP)40, reproducing the tandem-repeated epitope of the circumsporozoite protein of Plasmodium (Laverania) falciparum, was entrapped into murine, autologous erythrocytes by a hypotonic dialysis method. Mice immunized intravenously with minute amounts of encapsulated peptide produced considerable antibody titres. This result indicates that intraerythrocytic antigen administration may have a potential as an immunization system for humans, since it dispenses with adjuvants and carrier molecules.

Animals↗

The in vitro adherence of murine eosinophils, neutrophils and non-induced and induced macrophages to infective larvae of Toxocara canis (Nematoda, Ascarididae).

Infective larvae of the parasite nematode Toxocara canis were incubated in vitro with murine eosinophils, neutrophils and non-induced and induced macrophages. The interactions between the different types of cells and the worms were observed in the presence or absence of immune mouse serum and/or complement. Cells showed considerable differences in the manner, duration and outcome of this interaction. Despite the adhesion of cells to the larvae of T. canis, there was no evidence of damage to the worms. Scanning and transmission electron microscopic observations suggest that the cells adhere to the cuticular surface via an electron-dense material. This material might play a protective role against the helmintotoxic capacity of the inflammatory cells.

Animals↗