Biomedical subjects

E Santiago

Publications and source records attributed to E Santiago.

At least 19 recordsLinked to original sources

PubMed1992

New indole and triazino[5,4-b]indol-4-one derivatives: synthesis and studies as inotropics and inhibitors of blood platelet aggregation.

New triazino[5,4-b]indol-4-one derivatives carrying amino groups in position 3 were synthetized and tested as inotropic agents and inhibitors of platelet aggregation. 2h, 2p, 5p, and 6g are the most active as inotropic agents. Compounds were tested as inhibitors of platelet aggregation induced by adenosine 5'-diphosphate (ADP) and arachidonic acid (AA) (guinea pig whole blood). 2k, 2p, 5o, 6d, 6m, and 6o are the most active as inhibitors of the platelet aggregation induced by AA. 6d, 6h, and 6o are most active compounds also in the aggregation induced by ADP. Radioimmunoassay studies, following AA induced aggregation, measuring thromboxane B2 (TXB2) and prostaglandin E2 (PGE2) were carried out on compounds 2b, 2d, 2f, 2g, 2h, 2i, 2k, 2m, 2o, 2p, 2r, 5i, 5j, 5k, 5r, and 5f, which inhibit platelet aggregation induced by AA. None of the compounds tested turned out to be selective inhibitors. Compounds 2h and 2p showed both inotropic and platelet aggregation inhibiting activity.

Animals↗

PubMed1992

o-Iodosobenzoic oxidation and cleavage of myosin subfragment 1.

1. o-Iodosobenzoic acid (IOB) caused the formation of a disulfide bridge between SH1 and SH2 groups of myosin SF1 rendering inactive its ATPase activity. 2. IOB at high concentrations provoked fragmentation of SF1 at its tryptophan residues. 3. The main fragmentation point was located at 15 K from the amino terminus of the myosin heavy chain. 4. Actin was not fragmented by IOB. It protected SF1 tryptophans from IOB attack. 5. These results suggest a possible use of IOB as a reagent to study protein tryptophan under nondenaturing conditions.

Actins↗

PubMed1992

The distribution of spontaneous mutations on quantitative traits and fitness in Drosophila melanogaster.

Starting from a completely homozygous population of Drosophila melanogaster, two groups of 100 inbred lines each were established and maintained for 46 generations, by a single brother-sister mating and two double first cousin matings, respectively. Sternopleural bristle number, wing length and wing width were simultaneously scored in all lines every 4-5 generations. The means of four lines in each group departed significantly from the overall mean and, in each case, this was attributed to a single mutation of relatively large effect on at least one trait (0.3-1.4 environmental standard deviations in absolute value). Further analyses revealed widespread pleiotropy, similar gene action of a given mutation for all traits affected, and predominant additive action. No apparent association was found between the magnitudes of mutational effects on the traits and fitness. However, all recessive mutations were deleterious. The distribution of mutant effects was asymmetrical (positive for bristles and negative for wing measurements). Moreover, these distributions had a high variance and may be leptokurtic, due to the presence of major genes. Estimates of the ratio of new mutational variance to environmental variance ranged within (0.7-3.4) x 10(-3), those for wing measurements being generally larger. In agreement with theory, the rate of between-line differentiation was independent of population size.

Animals↗

PubMed1992

Conformational changes of S-1 related to its dissociation from actin.

The peptide pattern obtained after proteolysis of S-1 with trypsin was different in the absence or presence of anions. The affinity of tryptic and undigested S-1 for anions (CN-, SCN- or HCO3-) was different, as reflected by the altered values of Ki or Ka obtained from ATPase activity measurements. Anions CN-, SCN-, HCO3-, or PPi induced dissociation of actomyosin when added to acto-S-1 or acto-heavy-meromyosin. Among nucleoside di- and triphosphates, only triphosphates were effective with regard to the dissociation. The results suggest the existence of a regulatory site of cationic nature on S-1, which might be involved in the dissociation of actin from myosin.

Actins↗

PubMed1991

New 5H-pyridazino[4,5-b]indole derivatives. Synthesis and studies as inhibitors of blood platelet aggregation and inotropics.

Some fused 5H-pyridazino[4,5-b]indoles (7-10), substituted in positions 1 and 4 by hydrazine and/or amino groups, have been synthesized. These new compounds present a planar topography, a dipole with an adjacent acidic proton, and a basic hydrogen-acceptor site opposite the dipole. These compounds have some resemblance to carbazeram and other pyridazino agents with cardiotonic activity. Some of the new compounds here described possess inotropic activity (Table I and II), with a complementary effect as inhibitors of platelet aggregation (Table III and IV). 1-Hydrazino-4-(3,5-dimethyl)-1-pyrazolyl-5H-pyridazino[4,5-b ]indole hydrochloride (7a.HCl) is the first compound described in the literature with activities as inhibitor of PDE-IV and as selective inhibitor of TXA2 synthetase (Table V).

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1991

HIV-1 seropositive women in the Philippines: pregnancy outcome and perinatal transmission of HIV-1.

Annual surveillance studies were initiated in 1985 to determine the incidence and prevalence of HIV-1 infection in female prostitutes registered through the Social Hygiene Clinic System of the Philippine Department of Health. All of the confirmed HIV-1 seropositive women detected in the above surveys who could be contacted were followed up about every three months to monitor their clinical and immunological status. Since we regularly interviewed and examined these HIV-1 seropositive women, we were able to note the occurrence of pregnancies following HIV diagnosis. By September 1990, 54 HIV-1 seropositive women (aged 18-35) detected from the above surveys had been interviewed and examined. Twenty-six of these HIV-1 positive women had a total of 37 pregnancies. Eight were pregnant at the time of HIV diagnosis: three term deliveries, one premature delivery (PD) at eight months, three abortions, and one lost to follow-up while still pregnant. Five of these eight had repeat pregnancies: two term deliveries, two abortions, and one lost to follow-up while pregnant. Eighteen other women became pregnant one or more times after HIV diagnosis: seven term deliveries, 13 abortions, two PDs, one ectopic pregnancy terminated, one currently pregnant, and one lost to follow-up during pregnancy. There was no clear indication from clinical examinations and CD4+ cell counts that pregnancy exacerbated the course of HIV-1 related disease in these women. One of the 12 term infants has died and eight have developed non-specific findings that are suggestive but not diagnostic of HIV infection.2+ strongly seropositive by both ELISA and Western blot assay at 16 months.

Adult↗

PubMed1990

Modification of skeletal S-1 with fluorescein isothiocyanate.

1. Pyridoxal-5'-phosphate (PLP), a marker of primary amines, bound covalently to S-1 in an approximate ratio of 1:1. PLP was localized within the tryptic 25,000 mol. wt fragment. 2. Fluorescein isothiocyanate (FITC), which is known to bind covalently to primary amino groups located at nucleotide binding sites, readily bound to S-1 in a 2:1 ratio. FITC was localized within the 20,000 and 50,000 mol. wt tryptic peptides, in a ratio of 1:1 in each one. 3. These results are consistent with the existence of nucleotide binding sites on myosin different from those of the catalytic sites.

Adenosine Triphosphate↗

PubMed1990

Evidence that G-CSF is a fibroblast growth factor that induces granulocytes to increase phagocytosis and to present a mature morphology, and that macrophages secrete 45-kd molecules with these activities as well as with G-CSF-like activity.

Evidence is provided that conditioned medium from a macrophage-like cell line contains molecules of approximately 45 kd molecular weight with granulocyte colony-stimulating factor (G-CSF)-like activity as well as with the property of inducing granulocytes to phagocytose latex particles and to mature morphologically. This type of differentiation was found to be induced on either bone marrow or induced granulocytes, but not on resident or induced macrophages. On the other hand, resident but not induced macrophages are shown to induce these types of activities when challenged by bacterial lipopolysaccharides. Evidence that macrophages produce a factor that is mitogenic for fibroblasts is also provided. This activity was measured by the induction of increased proliferation by either low-density or saturated cultures of fibroblasts. Human recombinant G-CSF was employed and found also to possess these dual capabilities of inducing both the proliferation and differentiation of granulocytes as well as the proliferation of fibroblasts. Finally, a mechanism for the regulation of myeloid cell production and differentiation is described in which G-CSF produced by macrophages not only induces granulocytes to differentiate but induces fibroblasts to proliferate and secrete macrophage colony-stimulating factor (M-CSF), which in turn makes myeloid monocyte precursors proliferate and secrete more G-CSF.

Animals↗

PubMed1989

Effect of redox potential on rat liver F1-ATPase.

Redox titration of F1-ATPase from rat liver mitochondria referred to the modification of the hydrolytic activity on Mg-ATP has resulted in a three-step pattern, with three distinct jumps of activity separated by clear plateaus. The measured potentials ranged from -400 mV to +400 mV and were obtained by the addition of dithionite and ferricyanide. Electron exchange was facilitated with a mixture of different redox mediators. At pH 7.4 the midpoint potentials were +210 mV, +40 mV and -230 mV. These three midpoint potentials were displaced towards more negative values by 2,4-dinitrophenol or by an increase of the pH of the medium. The titration curves were described by n = 2 Nernst equations.

Animals↗

PubMed1989

Evidences that fibroblasts and epithelial cells produce a specific type of macrophage and granulocyte inducer, also known as colony-stimulating factor, and that monocyte-macrophages can produce another factor with proliferative inducing activity on myeloid cells and differentiative activity on macrophages.

Molecules with the property to induce proliferation of bone marrow cells in liquid cultures, and with colony-stimulating activity, were found on media conditioned (MC) by lung fibroblasts and kidney epithelial cells. These factors presented an apparent mol wt of 70,000 and 22,000 d respectively. Also when MC by epithelial cells from lungs was tested for the induction of proliferation of bone marrow cells a molecule with 22,000 d was detected. These molecules are thought to be CSF because they induce colony formation, and they are also similar in mol wt to two of the already known CSF. In fact the GM-CSF obtained from endotoxic lungs with a large epithelial cell content has a mot wt of 22,000 d, and the CSF-1 produced by a fibroblast cell line had 70,000. When the MC by fibroblast was used to induce bone marrow cells to proliferate, three new molecules with colony-stimulating activity were secreted. These molecules with apparent mol wts of 45,000, 30,000 and 17,000 d were also found in the MC by bone marrow cells when induced to proliferate with MC by epithelial cells. When the 45,000-d molecules was used in induced bone marrow cells to proliferate, once again the 30,000- and the 17,000-d molecules were secreted. Evidence is also provided that the 45,000-d molecule is produced by the monocyte-macrophage cells, and that it can induce Fc receptors or resident and elicited peritoneal macrophages. The possibility that the production of CSF is cell specific is discussed together with two models to explain the way in which these molecules can participate as proliferative (MGI-1) and differentiative (MGI-2) function in normal myeloid cell differentiation. Finally, a new terminology is proposed to classify this family of molecules.

Animals↗

PubMed1989

Nucleotide regulatory sites on skeletal myosin.

Myosin Ca2+-ATPase activity decreased in the presence of ADP. Free ATP acted either as an activator or as an inhibitor depending on its concentration. The inhibition caused by ADP or ATP followed a competitive pattern with respect to the substrate. ATP, at activating concentrations, competed with dinitrophenol and with the anions SCN-, CN- and HCO3- for the same binding sites of myosin, whereas ADP did not compete with them. These results suggest that the nucleotide regulatory site or sites, different from the hydrolytic sites, seem to coincide with the anion binding sites.

Adenosine Diphosphate↗

PubMed1989

Effect of reducing agents and uncouplers on the electrical potential generated by mitochondrial ATPase activity.

Beef heart submitochondrial particles bound to phospholipids impregnated filters generated an electrical potential upon the addition of ATP. The magnitude of the electrical potential reached depended on the phospholipid mixture composition used for filter impregnation, phosphatidylethanolamine being the active component for the electrical potential generation. Uncoupler FCCP (p-trifluoromethoxy carbonyl cyanide phenylhydrazone) inhibited the transmembrane electrical potential generation by diminishing the electrical resistance of the system as a result of its protonophoric action. However, uncouplers 2, 4-dinitrophenol and dicoumarol did not provoke large modifications of the electrical resistance under the conditions of pH and concentration used, and their action varied with the time elapsed after the submitochondrial particles purification, favouring the idea of the uncoupler interaction with a specific site on the membrane. Addition of sodium dithionite resulted in a higher plateau value for the electrical potential consistent with the promoted increase in ATPase activity. The effect of this agent was reversed by the 2,6-dichlorophenol-indophenol added at equivalent concentrations.

Animals↗

PubMed1989

Evidence that the macrophage-granulocyte inducer (MGI) is produced during cell proliferation, stored in G0, released in G1, cell specific, and induces the secretion of other colony-stimulating activities (CSA).

The secretion of the macrophage and granulocyte inducer (MGI), also known as colony-stimulating factor (CSF), by epithelial cells from lungs and kidneys, and by fibroblasts from lungs, was determined as a function of time in culture; it was found to be secreted during the initial exponential proliferation period, and not when the cells approached saturation density. When the cells were again induced to proliferate, large amounts of CSF were released after 3 h, thus hinting at the existence of a reserve pool. A CSF activity of 70,000 daltons was found in cultures of fibroblasts from lungs, kidneys, and the peritoneal cavity, a 45,000-dalton CSF was obtained from mouse peritoneal macrophages, and from bone marrow cells when activated for macrophage proliferation, and a 22,000-dalton CSF was found from epithelial cells, thus suggesting that the different CSFs are cell specific. When fibroblast CSF was used to induce bone marrow cells, three new molecules with colony-stimulating activity were produced, of 45,000, 30,000, and 17,000 daltons. The fraction with the 17,000-dalton activity also contained interleukin 1 activity, hinting at an indirect induction of colony formation by this factor. Finally the possible existence of a cascade reaction in which one CSF induces the appearance of other CSFs during the normal regulation of myeloid cell differentiation is discussed.

Animals↗

PubMed1989

[Metal ions in the insulin-receptor interaction in human erythrocytes].

The kinetics of insulin binding to its receptors on human erythrocytes suggests the existence of two types of receptors exhibiting negative cooperativity upon the binding of the hormone. Solubilized and purified receptors were associated to Zn++ or Cu++. The addition of these ions to erythrocytes or to purified insulin receptors from human erythrocytes resulted in an increase of specific insulin binding. Dialysis of solubilized or purified receptors against chelating agents such as EDTA or 1, 10-phenanthroline resulted in a decrease in specific binding of insulin. With the readdition of Zn++ or Cu++ to the medium an increase in specific binding was observed, and values much higher than those of the original preparations were obtained. Dialysis of purified receptors against chelating agents resulted in a decrease in the content of Zn++ and Cu++. These results suggest the possible involvement of a metal ion associated to the receptor in the formation of the insulin-receptor complex.

Adolescent↗

PubMed1988

Placebo-controlled trial of intravenous penicillin for severe and late leptospirosis.

The effect of a 7-day course of intravenous penicillin (6 million units/day) on severe, advanced leptospirosis was examined in a randomised, placebo-controlled, double-blind trial involving 42 patients. Every measurable aspect of the disease was favourably affected by penicillin. Fever lasted more than twice as long in the placebo group (11.6 [SD 8.34] days vs 4.7 [4.19] days, p less than 0.005), and by the fourth day after starting penicillin more than half the treatment group, but only 1 of 19 in the placebo group, were afebrile (p less than 0.005). Creatinine rises persisted more than thrice as long in the patients receiving only placebo (8.3 [8.46] days vs 2.7 [1.90] days; p less than 0.01). Penicillin also shortened the hospital stay and prevented leptospiruria. Intravenous penicillin should be given to patients with severe leptospirosis, even if therapy can be begun only late in the course of their disease.

Adolescent↗

PubMed1988

Interaction of F1-ATPase and its inhibitor peptide. Effect of pH.

1. The inhibition of F1-ATPase by its natural peptide inhibitor is mixed non-competitive with two pH optimum values (5.5 and 8.2). 2. A two-step model for the interaction is suggested in which two enzyme conformations would exhibit different affinities for the peptide. 3. At low pH, interaction would be favoured. At high pH, a conformation (not susceptible to inhibition) changes into another (susceptible to inhibition) through the hydrolytic reaction stimulation, due to high pH.

Animals↗

PubMed1988

Interaction of F1-ATPase and its inhibitor peptide. Effect of dinitrophenol, nucleotides and anions.

1. ATPase natural inhibitor interacted in a mixed non-competitive manner with compounds affecting hydrolytic activity. 2. Ka's for DNP, HCO3- and free ATP, and Ki's for SCN- and ADP became smaller as inhibitor peptide concentration increased, reflecting an increase in affinity of F1-ATPase for these compounds induced by the peptide. 3. Activators increased the peptide inhibitory effect, whereas inhibitors decreased it. 4. A two-step model for the peptide-enzyme interaction is suggested in which ATP hydrolysis is a key factor.

2,4-Dinitrophenol↗

PubMed1987

Regulatory sites of cationic nature on skeletal myosin.

The kinetics of the Ca2+-ATPase of chicken skeletal myosin has been found to be of a biphasic type. DNP and SCN- increased Ca2+-ATPase activity, whereas CN- and HCO3- acted as inhibitors in the concentration range used. Upon raising substrate concentration, activation and inhibition constants for those modifiers responded also with an elevation of their values.

2,4-Dinitrophenol↗