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Biomedical subjects

E Santiago

Publications and source records attributed to E Santiago.

At least 19 recordsLinked to original sources
PubMed2003

EEG and behavioral changes following neurofeedback treatment in learning disabled children.

Neurofeedback (NFB) is an operant conditioning procedure, by which the subject learns to control his/her EEG activity. On one hand, Learning Disabled (LD) children have higher values of theta EEG absolute and relative power than normal children, and on the other hand, it has been shown that minimum alpha absolute power is necessary for adequate performance. Ten LD children were selected with higher than normal ratios of theta to alpha absolute power (theta/alpha). The Test Of Variables of Attention (TOVA) was applied. Children were divided into two groups in order to maintain similar IQ values, TOVA values, socioeconomical status, and gender for each group. In the experimental group, NFB was applied in the region with highest ratio, triggering a sound each time the ratio fell below a threshold value. Noncontingent reinforcement was given to the other group. Twenty half-hour sessions were applied, at a rate of 2 per week. At the end of the 20 sessions, TOVA, WISC and EEG were obtained. There was significant improvement in WISC performance in the experimental group that was not observed in the control group. EEG absolute power decreased in delta, theta, alpha and beta bands in the experimental group. Control children only showed a decrease in relative power in the delta band. All changes observed in the experimental group and not observed in the control group indicate better cognitive performance and the presence of greater EEG maturation in the experimental group, which suggests that changes were due not only to development but also to NFB treatment.

Behavior↗
PubMed2003

Human immunodeficiency virus in plasma and cervicovaginal secretions in Filipino women.

This study examined 30 HIV-infected women in Manila to assess the relationship between cervicovaginal and plasma HIV-1 viral load. An interview and gynaecologic examination was conducted and cervicovaginal lavage (CVL) and venous blood specimens were collected. HIV-1 RNA was detected in plasma samples of 24 patients (80%) and in CVL samples of 18 women (60%); 16 patients (53%) had detectable levels in both. CVL HIV-1 RNA was detectable in 75% of women (6/8) with plasma viral loads between 10,000 and 100,000 copies/mL and in 77% of women (10/13) with plasma viral loads higher than 100,000 copies/mL (P =0.0086). Among women with CD4 cell counts of less than 200, 200-500, and greater than 500/mm(3), CVL HIV-1 RNA was detected in 73%, 69%, and 17% of women, respectively (P =0.1428). HIV-1 RNA shedding in the genital tract was significantly associated with plasma viral load.

Adult↗
PubMed2002

Inhibitory effect against polymerase and ribonuclease activities of HIV-reverse transcriptase of the aqueous leaf extract of Terminalia triflora.

Dichloromethane, methanol and aqueous extracts from the leaves of Terminalia triflora were investigated for their inhibitory effect on polymerase and ribonuclease activities of HIV reverse transcriptase.The most potent activity was found in the aqueous extract, which inhibited both polymerase and ribonuclease activities of the enzyme with an IC50 of 1.6 micro g/mL and 1.8 micro g/mL respectively. The antiinfective activity of the extract was demonstrated in HLT4LacZ-IIIB cell culture with an IC50 of 1.0 micro g/mL. The extract was submitted to a purification process by extractive and chromatographic methods. The activity remained in the hydrophillic fraction. Tannins present in this active purified fraction, as determined by TLC and HPLC methods, could account for the anti HIV-RT activity found in the aqueous extract.

Anti-HIV Agents↗
PubMed2001

Granulocyte colony-stimulating factor induces neutrophils to secrete macrophage colony-stimulating factor.

In this work we provide evidence showing that granulocytes produce macrophage colony-stimulating factor (M-CSF) from the band cell stage and secrete this factor when induced to differentiate into polymorphonuclear cells by recombinant human granulocyte colony-stimulating factor (rhG-CSF). Using an enriched population of myeloid band cells from murine bone marrow, we identified the presence of M-CSF with a chromophore-labelled monoclonal anti-M-CSF antibody. Using ELISA we detected the secretion of M-CSF in the supernatants of cultures of enriched band cells when induced with rhG-CSF to differentiate into mature neutrophils. We also found that M-CSF is the only factor responsible for the colony forming activity in the supernatants and lysates of band cells treated with rhG-CSF.

Animals↗
PubMed2001

Factors affecting the dimerization of the p66 form of HIV-1 reverse transcriptase.

The association and dissociation of the homodimeric p66/p66 form of HIV-1 reverse transcriptase were investigated. The effects on the dimerization process of different salt concentrations, pH and the presence of a template/primer and nucleotide substrates were monitored by measuring polymerase activity and analytical size-exclusion HPLC. At submicromolar concentrations of enzyme and physiological salt concentrations, most of the enzyme exists in the inactive monomeric form. Increasing NaCl concentration from 0.05 to 1 M decreased the equilibrium dissociation constant from 2.0 to 0.34 microM. Analysis of the kinetics of the dimerization process indicated it followed a two-step mechanism, with rapid initial association of the two subunits to form an inactive homodimer followed by a slow isomerization step rendering the active enzyme form. The presence of poly(rA)/dT(20) decreased the equilibrium dissociation constant of the homodimer about 30-fold, while the addition of 5 microM dTTP had no effect. The kinetics of the process showed that the template/primer favored dimerization by binding to the inactive homodimer and promoting its isomerization to the active form. These results were confirmed by analyzing the reverse reaction, i.e. the dissociation of the enzyme, by dilution in a low-ionic-strength buffer. The results suggest that binding of immature HIV-1 reverse transcriptase to its natural template/primer may be relevant in both the dimerization process and the selection of its natural primer.

Base Sequence↗
PubMed2000

Molecular mechanisms of apoptosis induced by an immunomodulating peptide on human monocytes.

A short immunomodulating peptide (Pa) containing a defined structural motif present in a number of extracellular matrix proteins and autoantigens was found to stimulate human monocytes. Pa-induced apoptosis of isolated monocytes, as indicated by internucleosomal DNA cleavage, increased annexin V binding capacity and cleavage of caspase substrates, such as poly(ADP)ribosylpolymerase. In addition, Bcl-2 protein levels were downregulated during Pa-induced cell death. Nuclear extracts of monocytes incubated with Pa showed higher neutral, Ca(2+)-dependent DNase activity than those obtained from nontreated monocytes. Caspase inhibitors prevented Pa-induced apoptosis, Bcl-2 depletion, and DNase activation. Treatment of monocytes with Pa activated c-Jun N-terminal kinases and p38 kinase, in an acidic sphingomyelinase- and caspase-dependent fashion. Pa-induced apoptosis was blocked by selective inhibitors of p38 kinase (SB203580) and acidic sphingomyelinase (SR33557). These results indicate that JNK and p38 kinase stimulation as well as monocyte apoptosis induced by Pa could depend, at least in part, on early activation of acidic sphingomyelinase.

Adjuvants, Immunologic↗
PubMed2000

Sources of abnormal EEG activity in brain infarctions.

EEGs from 16 patients with stroke in three different stages of evolution were recorded. EEG sources were calculated every 0.39 Hz by frequency domain VARETA. The main source was within the delta band in 2 out of 4 chronic patients, and in 67% of the patients in the acute or subacute stages when edema (cytotoxic or vasogenic) was present. Moreover, all patients showed abnormal activity in the theta band. Sources of abnormal activity in cortical or corticosubcortical infarcts were located in the cortex, surrounding the lesion. At the site of the infarct, a decrease of EEG power was observed. Sources of abnormal theta power coincided with edema and/or ischemic penumbra.

Adult↗
PubMed2000

Correlation between profile of circulating mononuclear cells and clinical manifestations in patients with pemphigus vulgaris.

Phenotypes of 38 samples of mononuclear (PBMC) cells from 11 different patients with pemphigus vulgaris (PV) at different stages of the disease were explored looking for a possible relationship between cell immunity, mucocutaneous or mucosal lesion intensity and capacity of serum autoantibodies to elicit the disease in mice. PBMC from 5 patients with mucocutaneous lesions and sera with IgG capable of inducing the disease in neonatal mice had a high proportion of mature monocytes with CD14low DRhigh, and co-expressing CD16 and CD11b. In addition, a high proportion of CD19+CD5+ activated B cells and a very low proportion of naive CD4+CD45RA+ and CD8+CD11b+ T lymphocytes was observed. Monocytes from these patients expressed inducible nitric oxide synthase (iNOS). In contrast, PBMC from 6 patients, with lesions restricted to mucosal membranes and IgG lacking the capacity to induce the disease in mice, contained a high proportion of CD14high DRlow co-expressing CD16 circulating macrophages, CD8+CD11b+ T cells, and a low proportion of activated B lymphocytes. The results suggest a possible association between proportion of different antigen presenting cells (monocytes with high HLA-DR and low CD14 expression and activated B lymphocytes, or differentiated monocytes/macrophages), type of PV and capacity of serum autoantibodies to elicit the disease in mice.

Acantholysis↗
PubMed2000

New antiherpetic 1,3-phenylene derivatives, inhibitors of the interaction of the HSV-1 origin binding protein (OBP) with DNA.

The synthesis of new 1,3-phenylene derivatives and their preliminary evaluation as antivirals (Herpes simplex 1, HSV-1) whose antiherpetic activity can be related with the inhibition of the interaction of the origin binding protein (OBP) with the DNA are presented. The new compounds are adjusted to a previously defined common structural model, consisting of a central aromatic system, which presents two side chains of different lengths in relative position 1, 3; these chains are made up of atomic groups characterized by the alternation of positive and negative centers, situating differently substituted rings, preferably aromatic, at the ends of both chains. Some of these derivatives, such as N,N''-(4-methoxy-1,3-phenylene)bis[N'-(4-nitrophenyl)urea] (2c) or (1,3-phenylene)bis[N-(p-tolyl)aminosulfonyl] (11b), show antiherpetic activity related to the proposed mechanism.

Animals↗
PubMed1999

Contribution of phosphodiesterase isoenzymes and cyclic nucleotide efflux to the regulation of cyclic GMP levels in aortic smooth muscle cells.

Involvement of phosphodiesterase isoenzymes (PDEs) in guanosine-3',5'-cyclic monophosphate (cGMP) hydrolysis was analyzed in aortic smooth muscle cells. Four families of PDEs were separated from pig aorta: PDE1 (calcium-calmodulin-activated), PDE3 (cGMP-inhibited), PDE4 (adenosine 3',5'-cyclic monophosphate [cAMP]-specific), and PDE5 (cGMP-specific). Within this PDE complement, PDE1 and PDE5 mostly contributed to the hydrolysis of cGMP both in the presence and absence of calcium-calmodulin. The role of these isoenzymes in cGMP degradation was analyzed in primary cultures of porcine aortic smooth muscle cells after stimulation with sodium nitroprusside (SNP) or atrial natriuretic factor (ANF). Pretreatment with 10 microM zaprinast, a concentration that selectively inhibits PDE5, did not potentiate the SNP- or ANF-induced rise of cGMP, questioning the widespread opinion that only PDE5 accounts for cGMP hydrolysis in this tissue. Further evidence came from experiments assessing the effect of zaprinast or 3-isobutyl-1-methylxanthine at concentrations inhibiting both type 1 and type 5 isoenzymes, in which this potentiation was clearly seen. Contribution of cGMP egression to the control of intracellular cGMP levels after SNP or ANF stimulation was also investigated. Shortly after guanylate cyclase activation, extracellular cGMP levels surpassed intracellular levels. However, comparison of the amounts of cGMP extruded to the extracellular medium with those degraded by PDEs leads to the conclusion that efflux is of relatively minor importance in regulating intracellular cGMP levels. In cells made tolerant to SNP, selective PDE5 inhibition synergistically increased intra- and extracellular cGMP amounts after SNP stimulation. These results indicate a previously undescribed greater relevance of PDE5 after tolerance development in aortic smooth muscle cells.

Animals↗
PubMed1999

Co-expression of inducible nitric oxide synthase and arginases in different human monocyte subsets. Apoptosis regulated by endogenous NO.

Human monocyte subsets, isolated from cultures of mononuclear cells, or freshly obtained from patients with multiple sclerosis, Graves' disease or pemphigus vulgaris, differed in phenotype, apoptotic features, mRNA levels of arginase II (A-II) and the inducible form of nitric oxide synthase (iNOS). Liver-type arginase I mRNA was present in all subsets. Apoptosis was followed by the expression of T cell intracellular antigen (TIA) and the simultaneous detection of DNA stainability by propidium iodine and annexin V binding. Apoptosis was practically absent both in activated CD14(++)CD33(++)DR(++)CD25(++)CD69(++)CD71(++/+) CD16(-) cells, expressing A-II mRNA and having arginase activity, but not iNOS mRNA, and in not fully mature large CD14(++)CD16(+)CD23(+)DR(++) monocytes, expressing simultaneously both mRNAs and having both enzyme activities. However, differentiated small CD14(+/++)CD16(+)CD69(+)CD25(+/-)CD71(++)CD23(+) DR(++) monocytes, expressing high levels of iNOS mRNA, exhibited apoptotic signs. Amounts of NO synthesised by monocytes co-expressing iNOS and arginase changed with the addition of arginine or an iNOS inhibitor; in that case a correlation of NO production and apoptotic features was observed. Data suggest a regulatory role for endogenous NO in apoptosis of stimulated and differentiated monocytes, and also that iNOS and A-II, when simultaneously present, could control the production of NO as a consequence of their competition for arginine.

Antigens, CD↗
PubMed1999

Synthesis and anti-HIV-1 activities of new pyrimido[5,4-b]indoles.

A set of new pyrimido[5,4-b]indole derivatives that are structurally related to some non-nucleside HIV-1 reverse transcriptase inhibitors were synthesized and biologically evaluated for their activity as inhibitors of wild and mutant HIV-1 RT types in an 'in vitro' recombinant HIV-1 RT screening assay, as well as anti-infectives in HLT4lacZ-1IIIB cells. Preliminary structure-activity relationships suggest that activity is promoted by simultaneous substitution in positions 2 and 4, especially when chains of alkyldiamine type are present, and by electron-releasing substituents (methoxy) in positions 7 and 8. The inactivity or the very low activity of title derivatives does not suggest interest in AIDS therapy.

Anti-HIV Agents↗
PubMed1999

Argentine plant extracts active against polymerase and ribonuclease H activities of HIV-1 reverse transcriptase.

Lipophilic and hydrophilic extracts of four Argentine plants (Gamochaeta simplicaulis Cabr. 1, Achyrocline flaccida Wein. D. C. 2, Eupatorium buniifolium H. et A. 3, and Phyllanthus sellowianus Muell. Arg. 4) were examined in vitro for their ability to inhibit the polymerase and ribonuclease H (RNase H) activities of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) (wild and Y181C mutant types). The active extracts were also examined as inhibitors of viral replication in HLT4LacZ-1IIIB cell cultures, evaluating their cytotoxicity in parallel. Infusions 2I and 4I, among the crude extracts, showed the highest activity. These extracts were refractioned into four fractions; 2I4 and 4I4 were active as inhibitors of DNA-polymerase (wild and Y181C types) and RNase H activities. These fractions were potent as inhibitors of viral replication and were not cytotoxic. Refractionation of 2I4 yielded five new fractions, two of which, 2I4-4 and 2I4-5, showed notable activity. Refractionation of 4I4 yielded for new fractions; of these, 4I4-3 and 4I4-4 were active. The marked biological activity found in the infusion of A. flaccida and P. sellowianus makes them sufficiently attractive to be considered in the combined chemotherapy of the disease.

Anti-HIV Agents↗
PubMed1999

Spatial and semantic inhibitory processing in schizophrenia.

Two experiments assessed inhibitory mechanisms associated with the posterior and anterior attention networks in schizophrenia. Experiment 1 assessed the inhibition of return effect of the posterior network. Both healthy adults and schizophrenic adults showed inhibition of return, suggesting that this inhibitory mechanism of visual orienting is preserved in schizophrenia. Experiment 2 assessed semantic inhibition, which supposedly taps the anterior network, in a lexical-decision task. Healthy adults showed semantic inhibition effects in both visual fields. Schizophrenic adults showed semantic inhibition effects when targets were presented to the left visual field, involving the right hemisphere. However, semantic facilitation rather than inhibition was observed when targets were presented to the right visual field, involving the left hemisphere. These results reflect left hemisphere dysfunction associated with deficits in attentional control in schizophrenia.

Adult↗
PubMed1998

Inducible nitric oxide synthase (iNOS) expression in human monocytes triggered by beta-endorphin through an increase in cAMP.

Evidence suggesting a relationship between neuroendocrine and immune systems is steadily growing. We demonstrate now that inducible nitric oxide synthase (iNOS) is expressed in human peripheral blood monocytes after incubation of lymphomononuclear cells in the presence of beta-endorphin, a neuropeptide released by the pituitary in response to mental or physical stress or by activated lymphocytes. beta-endorphin raised cAMP level in monocytes. The possible relationship between cAMP and iNOS expression on monocytes was investigated. Immunostaining for iNOS decreased, when besides beta-endorphin an inhibitor of protein kinase A (H-89) was added to the medium at the beginning of the incubation. The cAMP level raised by beta-endorphin was lowered by naloxone, which also reduced slightly iNOS expression. These results clearly point to the monocyte as a link between neuroendocrine and immune systems, an observation of potential relevance in our understanding of how stress and autoimmunity could be interconnected.

Amino Acid Sequence↗
PubMed1998

Granule associated DNase in T4 and T8 lymphocytes from patients with autoimmune diseases.

The presence of a DNase activity associated with secretion granules was detected in T4 and T8 lymphocytes from patients with autoimmune diseases. This activity was much higher in primary biliary cirrhosis (PBC) than in Graves' disease (GD) and multiple sclerosis (MS) or in healthy subjects. This granule associated DNase activity was Ca(2+)-dependent, inhibited by Zn2+, and higher at low pH; its molecular weight corresponded to 66kDa; it was more active with double-strand than single-strand DNA. Judging from its properties this enzyme differed from the three types of endonucleases described as involved in DNA fragmentation (DNase I, DNase II and NUC18). Flow cytometry analysis of T lymphocytes showed that DNase activity associated with CD4+ lymphocyte granules correlated with the ratio CD4+CD45RO+/CD4+CD45RA+ (memory and cytotoxic cells/naive cells, inducers of suppression). In contrast, T8 lymphocyte DNase activity correlated with the proportion of CD4+ lymphocytes with CD4+CD45RA- phenotype (helpers and inducers of cytotoxicity). The possible role of this DNase activity in the mechanisms of lysis or apoptosis mediated by CTL is discussed. We suggest that this DNase activity could be implicated in some of the alterations of the autoimmune response depending on cytotoxic T lymphocytes or T cell inducers of apoptosis.

Adult↗