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Biomedical subjects

E Medina

Publications and source records attributed to E Medina.

At least 37 records · Page 2Linked to original sources
PubMed2000

Modulation of host immune responses stimulated by Salmonella vaccine carrier strains by using different promoters to drive the expression of the recombinant antigen.

We evaluated whether immune responses stimulated by Salmonella vaccine carriers can be modulated by using different promoters to drive antigen expression. Mice were orally immunized with strains transfected with plasmids carrying beta-galactosidase (beta-gal) under the control of either a constitutive or an in vivo-activated promoter. While alpha-gal-reactive IgG1, IgG2a, IgG2b and IgG3 were detected in sera of mice immunized with Salmonella expressing constitutively beta-gal, higher titers dominated by IgG2a and IgG2b were detected in sera when the in vivo-activated promoter was used. beta-gal-specific proliferative responses of spleen-derived CD4+ T lymphocytes were similar in both groups. However, CD4+ T lymphocytes from mice immunized with the constitutive promoter secreted IL-4, IL-5, IL-6, IL-10 and IFN-gamma (Th1/Th2 pattern), whereas CD4+ cells mainly secreted IFN-gamma (Th1 pattern) when the second construct was used. The spleens of all immunized mice contained beta-gal-reactive CD8+ CTL precursors. The vaccine prototypes were tested for their capacity to control seeding and/or development within the lung of an intravenously delivered aggressive fibrosarcoma transfected with beta-gal. Reduced metastasis and significantly increased mean survival times were observed in all vaccinated mice. However, protection was improved when the carrier expressed beta-gal upon infection (80 % versus 50% survival, p < 0.05).

Administration, Oral↗
PubMed2000

Modulation of immune responses following antigen administration by mucosal route.

Most microbial infections are either restricted to the mucosal membranes or the etiologic agents needed to transit the mucosa. Thus, it is desirable to stimulate a mucosal response following vaccination, to block both infection and disease development. Attenuated vaccine carriers mimic natural infections, triggering also mucosal responses. Similar results can be achieved by administering antigens with appropriate adjuvants. However, the delivery of antigens per se is not sufficient to engender a protective response. A successful immunization requires the elicitation of an appropriate type of immune response (e.g. antibodies vs. cell-mediated immunity, Th1 vs. Th2 helper pattern). Therefore, a successful vaccination strategy demands the choice of adequate antigens, and their appropriate delivery and/or formulation to promote the required quality of immune response. Different strategies to optimize the immune responses elicited following vaccine administration by the mucosal route are discussed.

Adjuvants, Immunologic↗
PubMed2000

Diagnosis of arterial injuries caused by penetrating trauma to the neck: comparison of helical CT angiography and conventional angiography.

PURPOSE: To determine the sensitivity and specificity of helical computed tomographic (CT) angiography in the diagnosis of carotid and vertebral arterial injuries caused by penetrating neck trauma. MATERIALS AND METHODS: A prospective study was conducted during 24 months in 60 patients with penetrating neck trauma who were referred for conventional angiography owing to clinical suspicion of arterial injury. In the patient population, 146 arteries (77 carotid, 69 vertebral) were studied by means of conventional angiography. In all patients, conventional angiography and helical CT angiography were completed within 6 hours. Two radiologists interpreted helical CT angiographic studies by means of consensus. Conventional angiography was the standard of reference for determining the sensitivity and specificity of helical CT angiography. RESULTS: Conventional angiograms showed arterial injuries in 10 (17%) of 60 patients. Conventional angiographic findings were arterial occlusion (n = 4), arteriovenous fistula (n = 2), pseudoaneurysm (n = 3), pseudoaneurysm with arteriovenous fistula (n = 1), and normal arteries (n = 136). Nine of 10 arterial injuries and all normal arteries were depicted adequately at helical CT angiography. Sensitivity of helical CT angiography was 90%, specificity was 100%, positive predictive value was 100%, and negative predictive value was 98%. CONCLUSION: The sensitivity and specificity of helical CT angiography are high for detection of major carotid and vertebral arterial injuries resulting from penetrating trauma.

Adolescent↗
PubMed2000

Environmental factors associated with blood lead levels in Venezuelan children.

A preliminary study explored the relative contribution of residential sources of lead exposure on mentally challenged children who attend "special education" institutions (GI) compared to a group of age and sex matched school children (G2). We captured descriptive information and analyzed demographic variables, personal and household information, medical effects, environmental exposure factors, and children habits. Home paint, dust, soil, and water sampling was conducted and blood lead (BPb) levels determined. Eighteen G1 and 20 G2 children were studied. The mean G1 BPb was 16.9 +/- 7.9 microg/dl and was significantly higher than that in G2. Fifty percent of G1 children had PbB >20 microg/dl and 72.2% were >10 microg/dl. Low muscular strength, decreased osteotendinose reflexes, fine and gross motricity, deficient equilibrium, and hipotonic muscular tone coincided with >18 microg/dl BPb levels. In 61.1% of G1 homes paint lead levels were higher than permissible levels and 33.3% had dust lead exceeding that level. The high BPb levels in G1 probably resulted from ingestion of household paint, dust, and soil via "hand-to-mouth" activity. Environmental exposure to lead can be an important source of lead intake by infants and children and could affect neurological development. This study provides new insights currently unavailable for these children in Venezuela.

Anthropometry↗
PubMed2000

[Breast cancer risk factors in women in Santiago, Chile].

BACKGROUND: Epidemiological studies suggest a relation between breast cancer, diet and life styles. AIM: To analyze the association between food patterns, obesity, smoking, alcohol consumption and breast cancer risk in women of Santiago. PATIENTS AND METHODS: A case-control study design (170 cases and 340 controls), matched by age and sex, was used. Through a food frequency questionnaire the average daily intake of vegetables, fruits, beta-carotene, vitamin A, C, E and fiber was analyzed. Other exposures to non-nutritional risks (parity, smoking, cancer history) were also studied. Conditional logistic regression was calculated to determine the odds ratio associated with variations in food and nutrient intake and non-nutritional factors. RESULTS: Cases had a greater BMI and a higher prevalence of obesity than controls (p < 0.02). No differences were observed in either group food patterns. The ORs for breast cancer associated with obesity and alcohol consumption were 1.65 (95% CI 1.06-2.64) and 1.61 (95% CI 1.06-2.54) respectively (p < 0.05). Multiparity had a protective effect with 0.66 less risk (95% CI 0.44-0.99). No protective effect associated to a greater intake of vegetables, fruits or natural antioxidants was observed. Multivariate analysis model disclosed obesity as a risk factor (OR 1.79, p < 0.02) and parity > or = 4 as protective (OR 0.62, p < 0.02). CONCLUSIONS: This study does not support a protective role for natural antioxidants against breast cancer but indicate a weak association with obesity.

Adult↗
PubMed2000

[Adult mortality in Chile].

BACKGROUND: The study of mortality of human groups is important to judge the health conditions of population. AIM: To study the main mortality features among Chilean adults. MATERIAL AND METHODS: Information about mortality in Chile from the Instituto nacional de Estadísticas and The World Health Organization, was analyzed. Data was expressed mainly as rates. RESULTS: Annual mortality risk among Chileans is 812 per 100,000 inhabitants and is low compared to the rest of Latin America. In the last 30 years it has decreased systematically at a rate of 1% per year in both genders. The risk of mortality caused by cerebrovascular disease, coronary heart disease, hepatic cirrhosis, gastric cancer and tuberculosis has decreased. On the other hand, the risk of mortality caused by diabetes, hypertension and lung, gallbladder, prostate and colorectal cancer has increased. Mortality varies from 604 per 100,000 in Atacama to 934 per 100,000 in Valparaiso. The most factor that influences this variation is population aging. Mean survival at the start of adulthood is 54 years in men and 61 years in women. At 60 years, the expectancy is 19 and 24 years respectively. Mean age of death in Chile was 71.5 years in 1998. Seventy six percent of deaths occurs in the elderly and 33%, in people of 80 years or more. CONCLUSIONS: Chile is one of the four Latin American countries with lower mortality risk. In the last 30 years, the main causes of deaths among adults, with exception of pneumonia, have decreased. Therefore health care of the adult is in the correct track (Rev Méd Chile 2000; 128: 1144-49).

Adult↗
PubMed1999

Fc-mediated nonspecific binding between fibronectin-binding protein I of Streptococcus pyogenes and human immunoglobulins.

Fibronectin-binding protein I (SfbI) from Streptococcus pyogenes plays a key role in bacterial adhesion to, and invasion of, eukaryotic cells. In addition, SfbI exhibits a considerable potential as mucosal adjuvant and can trigger polyclonal activation of B cells. Here, we report that SfbI is also capable of binding human IgG in a nonimmune fashion. SfbI was reactive with IgG1, IgG2, IgG3, and IgG4 isotypes (type IIo IgG-binding profile). The affinity constant (Kd) of the SfbI-IgG interaction was in the range of 1-2 x 10(-5) M. Further studies demonstrated that the SfbI binding was mediated by the Fc component of the IgG molecule. Experiments performed using purified recombinant proteins spanning different domains of SfbI showed that the IgG-binding activity was restricted to the fibronectin-binding domains, and in particular to the fibronectin-binding repeats. Finally, the presence of recombinant SfbI resulted in an impairment of both phagocytosis of IgG-coated RBCs and Ab-dependent cell cytotoxicity by macrophages. These results demonstrated for the first time that, in addition to its major role during the colonization process, SfbI may also favor bacterial immune evasion after the onset of the infection by interfering with host clearance mechanisms.

Adhesins, Bacterial↗
PubMed1999

Expression of urease does not affect the ability of Bordetella bronchiseptica to colonise and persist in the murine respiratory tract.

To investigate the role played by urease during the Bordetella bronchiseptica infection process, the ability to colonise and persist in the mouse respiratory tract of a urease-negative B. bronchiseptica BB7865 and a BB7865 derivative constitutively expressing urease was compared with that of the wild-type strain. The results obtained showed that neither constitutive expression nor abolishment of urease activity had any significant effect on the course of B. bronchiseptica infection. Therefore, under our experimental conditions, urease is not essential for B. bronchiseptica to colonise and persist within the murine host.

Animals↗
PubMed1999

Salmonella vaccine carrier strains: effective delivery system to trigger anti-tumor immunity by oral route.

Recombinant Salmonella strains expressing heterologous antigens can be delivered by oral route triggering the elicitation of efficient antigen-specific humoral, T helper and cytotoxic responses. The potential of attenuated Salmonella spp. to trigger anti-tumor immunity was evaluated for the first time by using beta-galactosidase (beta-gal) as a model tumor-associated antigen (TAA). Beta-gal was expressed in a Salmonella typhimurium aroA vaccine carrier strain either constitutively or under the control of a promoter activated upon infection. Oral immunization with both vaccine prototypes resulted in the elicitation of beta-gal-specific humoral and cell-mediated immunity. Although both strains were able to trigger antigen-specific CTL, responses were more efficient when the expression was controlled by the promoter activated upon infection. The anti-tumor efficacy of the stimulated response was validated by challenging vaccinated animals with an aggressive fibrosarcoma transfected with beta-gal, which operationally acts as a TAA. Both groups of vaccinated mice exhibited a significant reduction in tumor take and growth with respect to animals vaccinated with plasmidless carrier (p < 0.05). However, the overall efficiency was better in the group in which beta-gal was controlled by the in vivo-activated promoter (85% versus 54%; p < 0.05).

Administration, Oral↗
PubMed1999

Genetically susceptible mice remain proportionally more susceptible to tuberculosis after vaccination.

DBA/2 mice are much more susceptible to infection with Mycobacterium tuberculosis than major histocompatibility complex-compatible BALB/c mice. It is shown here that, although vaccination provided mice of both strains with a capacity to reduce the level of infection in their lungs, vaccinated DBA/2 mice remained much more susceptible in this organ than vaccinated BALB/c mice. Consequently, the former mice developed more lung pathology and died much earlier than the latter. On the other hand, colony-forming unit counts and histology suggest that vaccination provided mice of both strains with an increased and equal ability to express immunity in the liver and spleen, thereby indicating that they possessed equal systemic levels of vaccine-induced immunity at the time of M. tuberculosis challenge. The results indicate that inefficient expression of immunity in the lungs is likely to prove an obstacle to successful vaccination against tuberculosis in resistant and susceptible mouse strains, but more so in the latter strains.

Animals↗
PubMed1999

Protective immune response against Streptococcus pyogenes in mice after intranasal vaccination with the fibronectin-binding protein SfbI.

Despite the significant impact on human health of Streptococcus pyogenes, an efficacious vaccine has not yet been developed. Here, the potential as a vaccine candidate of a major streptococcal adhesin, the fibronectin-binding protein SfbI, was evaluated. Intranasal immunization of mice with either SfbI alone or coupled to cholera toxin B subunit (CTB) triggered efficient SfbI-specific humoral (mainly IgG) and lung mucosal (14% of total IgA) responses. CTB-immunized control mice were not protected against challenge with S. pyogenes (90%-100% lethality), whereas SfbI-vaccinated animals showed 80% and 90% protection against homologous and heterologous challenge, respectively. Multiple areas of consolidation with diffused cellular infiltrates (macrophages and neutrophils) were observed in lungs from control mice; the histologic structure was preserved in SfbI-vaccinated animals, which occasionally presented focal infiltrates confined to the perivascular, peribronchial, and subpleural areas. These results suggest that SfbI is a promising candidate for inclusion in acellular vaccines against S. pyogenes.

Adhesins, Bacterial↗
PubMed1999

Neurally mediated syncope: pathophysiology and implications for treatment.

Neurally mediated syncope may occur in patients whose hemodynamic picture does not fit the characteristics of orthostatic intolerance as described elsewhere in this issue. Nonetheless, patients who suffer from neurocardiogenic or vasovagal syncope may be seriously incapacitated by their episodes of syncope or presyncope. Although it has been assumed that vagal activation as a result of stimulation of ventricular mechanoreceptors is essential to the production of these episodes, several critical observations are presented that suggest that other mechanisms may also be operative in some patient subsets. In addition, evidence is presented that the sympathetic responses of many of these patients may be reduced rather than increased and that abnormal baroreflex responsiveness may also play an causative role. These findings suggest new avenues for therapy in this field in which carefully controlled, randomized, double-blind trials are scarce.

Autonomic Nervous System↗
PubMed1999

Spectral statistics and dynamics of Lévy matrices.

We study the spectral statistics and dynamics of a random matrix model where matrix elements are taken from power-law tailed distributions. Such distributions, labeled by a parameter mu, converge on the Lévy basin, giving the matrix model the label "Lévy matrix" [P. Cizeau and J. P. Bouchaud, Phys. Rev. E 50, 1810 (1994)]. Such matrices are interesting because their properties go beyond the Gaussian universality class and they model many physically relevant systems such as spin glasses with dipolar or Ruderman-Kittel-Kasuya-Yosida interactions, electronic systems with power-law decaying interactions, and the spectral behavior at the metal insulator transition. Regarding the density of states we extend previous work to reveal the sparse matrix limit as mu-->0. Furthermore, we find for 2 x 2 Lévy matrices that geometrical level repulsion is not affected by the distribution's broadness. Nevertheless, essential singularities particular to Lévy distributions for small arguments break geometrical repulsion and make it mu dependent. Level dynamics as a function of a symmetry breaking parameter gives new insight into the phases found by Cizeau and Bouchaud (CB). We map the phase diagram drawn qualitatively by CB by using the delta3 statistic. Finally we compute the conductance of each phase by using the Thouless formula, and find that the mixed phase separating conducting and insulating phases has a unique character.

Journal Article↗
PubMed1999

Pathogenicity island 2 mutants of Salmonella typhimurium are efficient carriers for heterologous antigens and enable modulation of immune responses.

The potential use as vaccine delivery system of Salmonella typhimurium strains harboring defined mutations in the sseC (HH104) and sseD (MvP101) genes, which encode putative effector proteins of the type III secretion system of Salmonella pathogenicity island 2, was evaluated and compared with that of the well-characterized aroA mutant strain SL7207 by using beta-galactosidase (beta-Gal) as a model antigen. When orally administered to immune-competent or gamma interferon-deficient (IFN-gamma-/-) BALB/c mice, both mutants were found to be highly attenuated (50% lethal dose, >10(9) bacteria). Both strains were also able to efficiently colonize and persist in Peyer's patches. Immunization with HH104 and MvP101 triggered beta-Gal-specific serum and mucosal antibody responses equivalent to or stronger than those observed in SL7207-immunized mice. Although immunoglobulin G2 (IgG2) serum antibodies were dominant in all groups, IgG1 was also significantly increased in mice vaccinated with MvP101 and SL7207. Comparable beta-Gal-specific IgA and IgG antibodies were detected in intestinal lavages from mice immunized with the different strains. Antigen-specific CD4(+) T-helper cells were generated after vaccination with all vaccine prototypes; however, responses were significantly more efficient when HH104 and MvP101 were used (P < 0.05). Significantly higher levels of IFN-gamma were produced by restimulated spleen cells from mice immunized with HH104 than from those vaccinated with the MvP101 or SL7207 derivatives (P </= 0.05). Interestingly, the three strains induced major histocompatibility complex class I-restricted CD8(+) cytotoxic T cells against beta-Gal; however, cytotoxic T-lymphocyte responses were significantly stronger after immunization with HH104 (P < 0.05). These novel S. typhimurium attenuated strains constitute promising delivery systems for vaccine antigens. The qualitative differences observed in the obtained responses with different carriers may be useful for those applications in which a targeted immunomodulation is required.

Animals↗
PubMed1998

Gene transfer in dendritic cells, induced by oral DNA vaccination with Salmonella typhimurium, results in protective immunity against a murine fibrosarcoma.

A live attenuated AroA- auxotrophic mutant of Salmonella typhimurium (SL7207) has been used as carrier for the pCMVbeta vector that contains the beta-galactosidase (beta-gal) gene under the control of the immediate early promoter of Cytomegalovirus (CMV). We tested whether orally administered bacterial carrier could enter and deliver the transgene to antigen-presenting cells (APCs) through the natural enteric route of infection and whether beta-gal expression could generate a protective response against an aggressive murine fibrosarcoma transduced with the beta-gal gene (F1.A11) that behaves operationally as a tumor-associated antigen. After three courses, at 15-day intervals, mice developed both cell-mediated and systemic humoral responses to beta-gal. Mice vaccinated with the Salmonella harboring pCMVbeta, but not with plasmid-less carrier, showed resistance to a challenge with F1.A11 cells. These experiments suggest that Salmonella-based DNA immunization allows us to specifically target antigen expression in vivo to APCs. To prove that the transgene is actually expressed by APCs as a function of an eukaryotic promoter, the green fluorescent protein (GFP) was placed under the control of either the eukariotic CMV or a prokaryotic promoter. Using cytofluorometric analysis, GFP was detected only in splenocytes of mice receiving a Salmonella carrier harboring GFP under the CMV promoter. These results indicate that transgene expression occurs because of a Salmonella-mediated gene transfer to eukaryotic cells. Finally, approximately 19% of the splenocytes expressed GFP. Among them, F4/80(+) macrophages and CD11cbright dendritic cells (DCs) were scored as positive for GFP expression. Extensive work has been performed trying to optimize the way to transfect DCs, ex vivo, with genes coding for relevant antigens. We show here, for the first time, that DCs can be directly and specifically transduced in vivo such to induce DNA vaccination against tumors.

Administration, Oral↗
PubMed1998

Fibronectin-binding protein I of Streptococcus pyogenes is a promising adjuvant for antigens delivered by mucosal route.

A common problem in human vaccinology is the limited availability of efficient and non-toxic adjuvants capable of promoting mucosal responses. The potential usefulness of fibronectin-binding protein I (Sfbl) of Streptococcus pyogenes as immunological adjuvant was assessed using ovalbumin (OVA) as a model antigen. Mice were immunized by intranasal route, either with soluble OVA or OVA covalently coupled to Sfbl. Immunization with OVA-Sfbl resulted in the elicitation of about 100-fold higher titers of anti-OVA serum IgG than using OVA alone. The anti-OVA IgG subclass pattern was dominated in both groups of mice by IgG1, followed by IgG2b, IgG2a, and IgG3. Immunization with OVA-Sfbl also resulted in the elicitation of OVA-specific IgA in lung washes (24% of the total IgA), which was absent in mice immunized with OVA alone. Spleen cells from OVA-Sfbl-immunized mice also gave a much stronger proliferative response to restimulation with soluble OVA in vitro. Phenotypic analysis of proliferating cells showed an enrichment in CD4+ T cells, producing a pattern of cytokines (IL-4, IL-5, IL-6 and IL-10) characteristic of Th2-type cells. In contrast to immunization with soluble OVA alone, OVA-Sfbl induced the generation of CD8+ OVA-specific cytotoxic cells. These results demonstrate that Sfbl represents a promising mucosal adjuvant able to substantially improve cellular, humoral and mucosal responses when coupled to an antigen administered by intranasal route.

Adhesins, Bacterial↗
PubMed1998

Attenuated Listeria monocytogenes carrier strains can deliver an HIV-1 gp120 T helper epitope to MHC class II-restricted human CD4+ T cells.

Listeria monocytogenes is a facultative intracellular pathogen which, following uptake by macrophages, escapes from the phagosome and replicates in the cytoplasm. This property has been exploited using recombinant L. monocytogenes as a carrier for the intracytoplasmic expression of antigens when MHC class I-restricted cytotoxic T lymphocyte responses are required. Much less is known of the ability of these bacteria to trigger MHC class II-restricted responses. Here, we demonstrate that after ingestion of L. monocytogenes expressing a T helper epitope from the gp120 envelope glycoprotein of HIV, human adherent macrophages and dendritic cells can process and present the epitope to a specific CD4+ T cell line in the context of MHC class II molecules. No significant differences were observed when the attenuated strains were trapped in the phagolysosome or impaired in the capacity to spread intracellularly or from cell to cell. Similar results were obtained using carrier proteins that were either secreted, associated with the bacterial surface, or restricted to the bacterial cytoplasm. A dominant expression of the TCR Vbeta 22 gene subfamily was observed in specific T cell lines generated after stimulation with the recombinant strains or with soluble gp120. Our data show that in this in vitro system L. monocytogenes can efficiently deliver antigens to the MHC class II pathway, in addition to the well-established MHC class I pathway. The eukaryotic cell compartment in which the antigen is synthesized, and the mode of display seem to play a minor role in the overall efficiency of epitope processing and presentation.

Antigen Presentation↗