Biomedical subjects

C A Vaz

Publications and source records attributed to C A Vaz.

At least 19 recordsLinked to original sources

PubMed2001

Observation of a bi-domain state and nucleation free switching in mesoscopic ring magnets.

We present the results of a study of the magnetic properties of an array of 34-nm thick Co(100) epitaxial ring magnets, with inner and outer diameters of d(in) = 1.3 microm and d(out) = 1.6 microm, respectively. Magnetic measurements and micromagnetic simulations show that a two step switching process occurs at high fields, indicating the existence of two different stable states. In addition to the vortex state, which occurs at intermediate fields, we have identified a new bi-domain state, which we term the onion state, corresponding to opposite circulation of the magnetization in each half of the ring. The onion state is stable at remanence and undergoes a simple and well characterized nucleation free switching.

Journal Article↗

PubMed2000

Resistance to Paracoccidioides brasiliensis infection is linked to a preferential Th1 immune response, whereas susceptibility is associated with absence of IFN-gamma production.

The secretion of interferon-gamma (IFN-gamma), interleukin-2 (IL-2), IL-4, IL-5, and IL-10 by antigen-stimulated lymph node cells, eosinophil maturation, and the antibody isotypes produced were examined during intraperitoneal infection of susceptible (B10.A) and resistant (A/Sn) mice with Paracoccidioides brasiliensis. Lymph node cells from resistant mice produced early and sustained levels of IFN-gamma and IL-2, whereas susceptible animals secreted low to undetectable amounts of these type 1 cytokines. Both mouse strains presented late and transient production of IL-4, whereas IL-10 was produced constantly throughout the course of disease. Resistant animals produced increasing levels of IL-5 in the chronic phase of the infection (from the eighth week on), whereas susceptible mice showed two peaks of IL-5 production, at the first and twelfth weeks after infection. Only the susceptible strain presented medullary and splenic eosinophilia concomitant with the raised IL-5 production. In resistant mice, the levels of IgG2a antibodies were significantly higher than those observed in susceptible mice, which preferentially secreted IgG2b and IgA isotypes. Taken together, these results demonstrate that a sustained production of IFN-gamma and IL-2 and a predominant secretion of IgG2a antibodies are associated with resistance to P. brasiliensis. In contrast, the production of low levels of IFN-gamma, early secretion of high levels of IL-5 and IL-10, eosinophilia, and a preferential secretion of IgG2b and IgA isotypes characterize the progressive disease in susceptible animals.

Animals↗

PubMed2000

Depletion of CD8(+) T cells in vivo impairs host defense of mice resistant and susceptible to pulmonary paracoccidioidomycosis.

Using a pulmonary model of infection, we demonstrated previously that A/Sn and B10.A mice are, respectively, resistant and susceptible to Paracoccidioides brasiliensis infection. Employing the same experimental model, we examined herein the role of CD8(+) T cells in the course of paracoccidioidomycosis. Treatment with anti-CD8 monoclonal antibodies caused a selective depletion of pulmonary and splenic CD8(+) T cells in both mouse strains. The number of pulmonary CD4(+) T cells and immunoglobulin-positive cells was independent of the number of CD8(+) T cells. In susceptible mice, the loss of CD8(+) T cells by in vivo treatment with anti-CD8 monoclonal antibodies impaired the clearance of yeasts from the lungs and increased the fungal dissemination to the liver and spleen. The same treatment in resistant mice increased fungal dissemination to extrapulmonary tissues but did not alter the pulmonary fungal load. Furthermore, CD8(+) T-cell depletion did not modify delayed-type hypersensitivity reactions of A/Sn mice but increased these reactions in B10.A mice. The production of P. brasiliensis-specific antibodies by resistant and susceptible mice depleted of CD8(+) T cells was similar to that of mice given control antibody. Histopathologically, depletion of CD8(+) T cells did not disorganize the focal granulomatous lesions developed by both mouse strains. These results indicate that CD8(+) T cells are necessary for optimal clearance of the fungus from tissues of mice infected with P. brasiliensis and demonstrate more prominent protective activity by those cells in the immune responses mounted by susceptible animals.

Animals↗

PubMed1998

Protective role of gamma interferon in experimental pulmonary paracoccidioidomycosis.

We have developed a murine model of pulmonary infection by Paracoccidioides brasiliensis in which resistance was associated with immunological activities governed by gamma interferon (IFN-gamma). To better characterize this model, we measured type 1 and type 2 cytokines in the lungs and investigated the effect of endogenous IFN-gamma depletion by monoclonal antibodies in the course of infection of susceptible (B10.A) and resistant (A/Sn) mice. At weeks 4 and 8 after infection, lungs from susceptible animals presented levels of IFN-gamma, interleukin-4 (IL-4), IL-5, and IL-10 higher than those in resistant mice. In both mouse strains, neutralization of endogenous IFN-gamma induced exacerbation of the pulmonary infection, earlier fungal dissemination to the liver and spleen, impairment of the specific cellular immune response resulting in significantly lower delayed-type hypersensitivity reactions, and increased levels of immunoglobulin G1 (IgG1)- and IgG2b-specific antibodies. Histopathological analysis demonstrated that depletion of IFN-gamma changes the focal granulomatous lesions found in the lungs of B10.A and A/Sn mice into coalescent granulomata which destroy the pulmonary architecture. These results suggest that irrespective of the mouse strain, IFN-gamma plays a protective role and that this cytokine is one major mediator of resistance against P. brasiliensis infection in mice.

Animals↗

PubMed1998

Comparative studies on the antibody repertoire produced by susceptible and resistant mice to virulent and nonvirulent Paracoccidioides brasiliensis isolates.

The specific recognition pattern of antibodies produced by susceptible and resistant mice infected with the low virulence Paracoccidioides brasiliensis isolate (Pb265) was examined by an immunoblotting procedure and compared with that of antibodies produced by highly virulent isolate (Pb18) in infected mice. Both mouse strains produced IgG antibodies to 13 of the 16 major antigen bands, and showed a recognition pattern similar to sera from mice infected with the virulent isolate. Nevertheless, the reaction to components interposed among major bands (intermediate antigen bands of 75, 73, 68, 64, 33, 23, 22, and 12.5 kD) were detected exclusively with antibodies raised in response to the virulent P. brasiliensis isolate independent of the resistance pattern of the host. It was also demonstrated here that the most diversified repertoire of specific IgA was produced when the susceptible host and virulent fungus were associated.

Animals↗

PubMed1996

Monoclonal antibodies against conserved epitopes of a 46-kDa protein from Neisseria meningitidis.

The purpose of the present study was to generate monoclonal antibodies (mAbs) against conserved epitopes of B meningococcus which could be applicable to the immunoscreening of bacterial meningitis. Three mAbs reactive to a 46-kDa protein conserved in eight sero-groups and several sero(sub)types of Neisseria meningitidis were selected for the present study. No reaction was detected with whole-cell lysates of Staphylococcus aureus. Streptococcus pneumoniae, Haemophilus influenzae type b or Escherichia coli. Two of these mAbs recognized 46-kDa epitopes in four other Neisseria spp, and the third, MC3.13, cross-reacted only with N. lactamica. All mAbs reacted with whole-cell lysates from a N. meningitidis mutant strain lacking the class 1 outer membrane protein (43-47 kDa). Immunoelectron microscopy revealed a cytoplasmic location for the 46-kDa protein. The MC3.13 monoclonal antibody is potentially applicable to a rapid screening of bacterial meningitis.

Animals↗

PubMed1995

Influence of the genetic pattern and sex of mice in experimental paracoccidioidomycosis.

Eight genetically different strains of mice were compared regarding the dissemination of Paracoccidioides brasiliensis to the lungs, liver and omentum/pancreas, DTH responses and specific antibody production at 16 weeks after intraperitoneal infection with Pb18, a virulent P. brasiliensis isolate. The degree of dissemination of the infection varied: B10.A and C57B1/6, the most susceptible mouse strains, had positive cultures and high colony-forming unit (CFU) counts in all analysed organs. DBA/2 and A/Sn mice had negative cultures, being thus classified as the most resistant strains. CBA/J, C3H/HeJ, F1(A/SnxB10.A) and BALB/c mice were regarded as relatively resistant, since discrete fungal growth was observed only in one or two of the studied organs. All mouse strains, except B10.A mice, produced specific DTH responses which did not seem to be associated with the severity of disease. Production of high levels of specific antibodies was found in all strains except in the DBA/2 and C57B1/6 mice. The influence of the host sex on the outcome of paracoccidioidomycosis was evident only in susceptible animals: female B10.A mice displayed lower CFU counts in the three examined organs, whereas no differences were found between male and female A/Sn animals. The higher resistance of female B10.A mice was not accompanied by differences in their capacity to maintain a DTH reaction, nor in their production of antibody. This fact argues against the widely believed association of susceptibility to P. brasiliensis infection with both impaired DTH reactivity and increased humoral response.

Animals↗

PubMed1995

Pulmonary paracoccidioidomycosis in resistant and susceptible mice: relationship among progression of infection, bronchoalveolar cell activation, cellular immune response, and specific isotype patterns.

Using the intraperitoneal route of infection, we demonstrated previously that A/Sn mice are resistant and B10.A mice are susceptible to Paracoccidioides brasiliensis infection. Since paracoccidioidomycosis is a deep systemic granulomatous disorder that involves primarily the lungs and then disseminates to other organs and systems, we herein investigated the course of the infection and the resulting immune responses developed by A/Sn and B10.A mice after intratracheal infection with P. brasiliensis yeast cells. It was observed that A/Sn mice develop a chronic benign pulmonary-restricted infection, whereas B10.A mice present a chronic progressive disseminated disease. A/Sn animals were able to restrict fungal infection to the lungs despite the increased fungal load at the beginning of the infection. This behavior was associated with low mortality rates, the presence of adequate and persistent delayed-type hypersensitivity reactions, oxidative burst by bronchoalveolar cells, and production of high levels of specific antibodies in which immunoglobulin G2a (IgG2a) and IgG3 isotype titers were significantly higher than those observed in the susceptible mice. In contrast, B10.A animals showed a constant pulmonary fungal load and dissemination to the liver and spleen. This infection pattern resulted in high mortality rates, discrete delayed-type hypersensitivity reactivity, poorly activated or nonactivated bronchoalveolar cells, and production of specific IgG2b isotype titers significantly higher than those observed in the resistant mice at week 4 of infection. Thus, A/Sn and B10.A mice maintain the same resistance patterns as those observed previously with the intraperitoneal route of infection. Furthermore, the obtained results suggest that resistance to paracoccidioidomycosis is associated with T-cell, macrophage, and B-cell activities that are known to be mediated by gamma interferon.

Animals↗

PubMed1994

Gelatinase activity of exoantigens from virulent and non-virulent isolates of Paracoccidioides brasiliensis.

Differences in the occurrence of components with gelatinase activity were detected among four isolates of Paracoccidioides brasiliensis: Pb339 and Pb18 (highly virulent), and Pb265 and Pb18AV (very low virulence). Culture filtrates from these isolates were electrophoresed in substrate gels and tested for gelatinase activity. Pb339 showed three enzyme bands of apparent molecular masses: 43, 53 and 78 kDa; Pb18 had two bands, one at 59 kDa and another with molecular mass higher than 78 kDa. Isolate Pb18AV showed only one band at 78 kDa and Pb265 exhibited a component of molecular mass which failed to enter the separating gel.

Antigens, Fungal↗

PubMed1994

Cytokines in the host response to mycotic agents.

In summary, different approaches have been taken to understand cytokine responses to different fungal infections. Singer-Vermes and co-investigators indirectly examined cytokine responses to paracoccidioidomycosis by studying the types of cellular and humoral immune responses that were induced in resistant and susceptible mouse strains. Their results implicated Th1 cell responses in the resistant mouse strain and Th2 cell responses in the mouse strain susceptible to paracoccidioidomycosis. By measuring cytokine production and through cytokine depletion experiments, Wu-Hsieh showed that besides IFN gamma, TNF alpha was important in host defences against the intracellular pathogen, H. capsulatum. Both cytokines play important roles in the regulation of other cytokines. In histoplasmosis, the dynamics of the complex interactions amongst cytokines govern the efficiency of host clearance of the fungus from tissues. Ferrante and collaborators, examining TNF alpha and TNF alpha receptors on neutrophils presented data showing that TNF alpha plays an important role in the activation of neutrophils for anti-Candida activity. Through the detection of cytokine mRNAs with RT-PCR, Moser and co-workers found that cytokine mRNAs of macrophage origin were produced preferentially in the lungs of mice infected with Histoplasma or Blastomyces. A great challenge still lies ahead of us. It is well understood that the interactions of cytokines are extremely complex at the levels of the induction and expression of the immune responses as well as on effects on natural cellular defences. Work accomplished thus far has laid the ground work for future studies in the effort to dissect host cytokine responses and to understand the roles of cytokines in protection against fungal infections.

Animals↗

PubMed1993

Orthonormal (Fourier and Walsh) models of time-varying evoked potentials in neurological injury.

Estimation of time-varying changes in evoked potentials (EP's) has important applications, such as monitoring high-risk neurosurgical procedures. We test the hypothesis that injury related changes in EP signals may be modeled by orthonormal basis functions. We evaluate two models of time-varying EP signals: the Fourier series model (FSM) and the Walsh function model (WFM). We estimate the Fourier and Walsh coefficients with the aid of an adaptive least-mean-squares technique. Results from computer simulations illustrate how selection of model order and of the adaptation rate of the estimator affect the signal-to-noise ratio (SNR). The FSM results in a somewhat higher steady-state SNR than does the WFM; however, the WFM is less computationally complex than is the FSM. We apply these two orthonormal functions to evaluate transient response to hypoxic hypoxia in anesthetized cats. Trends of the first five frequencies (Fourier) and sequencies (Walsh) show that the lower frequencies and sequencies may be sensitive indicators of hypoxic neurological injury.

Adaptation, Physiological↗

PubMed1993

Advances in experimental paracoccidioidomycosis using an isogenic murine model.

A genetically controlled murine model of paracoccidioidomycosis which allowed us to investigate several parameters of the host-parasite interactions was established in our laboratory. Natural resistance and acquired immune responses to P. brasiliensis infection were investigated employing resistant and susceptible mice infected with highly virulent or slightly virulent P. brasiliensis isolates. Resistant mice inoculated with a highly virulent P. brasiliensis isolate present efficient macrophage activation, presence of DTH response, low levels of specific antibody and a tendency to resolution of the infectious process, suggesting that a T helper-1 mode of immune response is mounted. Susceptible mice, on the contrary, seem to mount a predominantly T helper-2 type of immune response activation in which an inefficient macrophage activation, depressed DTH reactions and high levels of antibodies result in progressive disease. The crucial role of the fungal virulence on the outcome of the infection of susceptible and resistant mice is also demonstrated, thus reinforcing the idea that both the innate resistance of the host and the pathogenicity of the fungal cells are determinant on the outcome of the disease. This model is proposed as a framework of our current knowledge of the host-parasite interactions in paracoccidioidomycosis and as a basis for future challenge in continuing analyses.

Animals↗

PubMed1992

Specific recognition pattern of IgM and IgG antibodies produced in the course of experimental paracoccidioidomycosis.

Specific IgM and IgG responses to Paracoccidioides brasiliensis produced in resistant and susceptible mice during experimental paracoccidioidomycosis were examined by the immunoblotting procedure. Sera from infected mice recognized 51 antigen bands with apparent molecular masses from 8 to 86 kD. Sixteen of these were defined as major antigen bands because of almost universal presence of antibodies to them, and their intense staining. All sera, including those from normal control mice, tested for both IgM and IgG antibody reacted with the major E antigen which appeared as a large diffuse band from 43 to 47 kD. Comparisons between resistant and susceptible mice showed some significant differences in IgM responses to many antigen bands. While IgG responses were quite similar for both strains, differences were apparent in the response to the antigens at 62 and 68 kD.

Animals↗

PubMed1991

Cardiovascular, neuropeptide Y, and adrenergic responses in stress are sexually differentiated.

Cardiovascular and sympatho-adrenomedullary responsiveness at rest and during stress were studied in weight-matched, sexually mature male and female rats. At rest, although there were no sex differences in cardiovascular parameters, females had two-fold higher plasma levels of norepinephrine (NE) and epinephrine. Resting plasma levels of neuropeptide Y-immunoreactivity (NPY-ir, a putative sympathetic cotransmitter and a vasoconstrictor) were similar in both sexes. Stresses of handling and cold (4 degrees C) water exposure induced greater pressor and tachycardic responses in males than in females. Males but not females exhibited a protracted recovery from the stress-induced pressor responses and a 2-fold increase in plasma NPY-ir suggesting that NPY release is sexually differentiated. Only in males, low basal plasma NE and NPY-ir levels inversely correlated with greater cold-induced pressor responses. Furthermore, in areflexic pithed rats, pressor adrenergic and NPY responses were greater in males than in females suggesting the possibility of "down"-regulation of vascular adrenergic receptors in females (due to elevated circulating catecholamines) and "up"-regulation of NPY and adrenergic receptors in males.

Adrenergic Fibers↗

PubMed1990

Norepinephrine and neuropeptide Y: vasoconstrictor cooperation in vivo and in vitro.

Norepinephrine (NE)-evoked vasoconstrictor and pressor responses are reduced after prolonged exposure; such desensitization is observed both clinically and experimentally. The vasoconstrictor neuropeptide Y (NPY) coexists with NE in perivascular sympathetic nerves, and the results of both in vivo and in vitro studies have indicated functional cooperation between NE and NPY. We propose that NPY becomes increasingly important in situations of high sympathetic activity associated with blunted NE responses. Prolonged NE infusion in conscious rats resulted in adrenergic desensitization; however, NPY administration restored the responsiveness to NE. In naive rats, NE greatly enhanced the pressor action of NPY. An analogous phenomenon was observed in the rabbit isolated pulmonary artery, which failed to respond to NPY unless preexposed to NE; this action of NE was only partly inhibited by conventional adrenoceptor and Ca2+ influx blockade. Conversely, NPY enhanced NE-evoked constriction, in particular when the alpha-adrenoceptor reserve was eliminated. It is proposed that threshold synergism, in part caused by converging stimulation of phospholipase C, accounts for much of the NPY/NE cooperativity. We conclude that 1) NPY and NE cooperate to produce vasoconstriction, both in vivo and in vitro; 2) NPY has the capacity to reverse adrenergic desensitization but not vice versa; 3) NE enhances NPY-evoked vasoconstriction, in part independently of conventional adrenoceptor blockade; 4) threshold synergism phenomena, but not "receptor-receptor interactions," account for (most of) the observed NPY/NE cooperation; and 5) when present, alpha-adrenoceptor reserve prevents the lowering of the NE threshold by NPY.

Adrenergic alpha-Agonists↗

PubMed1989

Adaptive Fourier estimation of time-varying evoked potentials.

An estimation procedure for dealing with time-varying evoked potentials is presented here. The evoked response is modeled as a dynamic Fourier series and the Fourier coefficients are estimated adaptively by the least mean square algorithm. Approximate expressions have been developed for the estimation error and time constant of adaptation. A procedure for optimizing the estimator performance is also presented. The effectiveness of the estimator in dealing with simulated as well as actual evoked responses is demonstrated.

Evoked Potentials, Visual↗

PubMed1988

Release of immunoreactive-neuropeptide by rat platelets.

Neuropeptide Y, a potent vasoconstrictor and cardiac depressant, is re-leased from sympathetic nerve endings. Its presence in megakaryocytes suggests this peptide might be stored in platelet granules and released during aggregation. Immunoreactive-neuropeptide Y was measured in platelet rich and platelet poor plasma, and was substantially greater in the former. Addition of collagen to platelets resulted in release of neuropeptide Y which paralleled, in a concentration-dependent manner, the degree of platelet aggregation. Adenosine diphosphate, at concentrations which induce only the first phase of aggregation and not the release reaction, caused only a minor release of neuropeptide Y. These results suggest that platelet release could be a major source of circulating neuropeptide Y and could contribute to hemodynamics of pathophysiological states involving platelet activation.

Adenosine Diphosphate↗

PubMedDate not supplied

Adaptive Fourier series modeling of time-varying evoked potentials: study of human somatosensory evoked response to etomidate anesthetic.

Evoked potentials (EPs) have traditionally been analyzed in time domain, with amplitude and latency of various signal components used in clinical interpretation. A new approach, called adaptive Fourier series modeling (FSM), is presented here. Dynamic changes in magnitudes of Fourier coefficients are analyzed for diagnostic purposes. In order to estimate the time-varying changes in the Fourier coefficients of noisy signals, a least mean-square filtering algorithm is applied. Results of computer simulations as well as experimental data are presented. Time-varying trends are presented in a new compressed evoked spectrum format. These techniques are applied to the study of alterations in human somatosensory EPs caused by the intravenous administration of etomidate during neurosurgical procedures. Amplitude increases of the order of 200-500% occurring within a time span of about 100 sec were captured. Due to its superior convergence properties, the adaptive FSM technique estimates more rapid changes in amplitude and latency than exponentially weighted averaging or moving window averaging schemes.

Computer Simulation↗