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Biomedical subjects

B A Torres

Publications and source records attributed to B A Torres.

At least 19 recordsLinked to original sources
PubMed1991

Sudden infant death syndrome. Comparison of incidence in four urban Florida counties.

The observed incidence of sudden infant death syndrome (SIDS) in Hillsborough County is significantly higher than corrected rates in three other metropolitan areas of the state which have common demographic features. An eight year analysis of data (1979-1986) demonstrates the consistency of the observation. Since SIDS is a postmortem diagnosis of exclusion utilized for deaths of infants for whom no anatomic or biochemical cause can be determined and represents a large segment of deaths between 28 days and one year of age, there is a need to assure that all areas of the state utilize similar criteria for assignment of the diagnosis.

Cause of Death↗
PubMed1990

Arginine vasopressin-binding peptides derived from the bovine and rat genomes differ in their abilities to block arginine vasopressin modulation of murine immune function.

Previously we reported on a nonapeptide (binding peptide) derived by reading the complementary DNA strand of the bovine arginine vasopressin (AVP) gene in the 3'5' direction that specifically blocks the AVP helper signal for gamma-interferon (IFN gamma) production by helper cell-depleted mouse spleen cultures. Bovine 5'3' AVP-binding peptide, however, did not block AVP activity. We report here on the relative abilities of 5'3' and 3'5' AVP-binding peptides derived from the bovine and rat AVP genes to block the AVP helper signal for IFN gamma production. The sequences of the bovine and rat 5'3' AVP-binding peptides differ by two amino acids, whereas the 3'5' AVP-binding peptides derived from both genes are the same. In contrast to the lack of blocking activity of the bovine 5'3' AVP-binding peptide, the rat 5'3' AVP-binding peptide was almost as effective as the 3'5' AVP-binding peptide in blocking AVP function. No effect was seen with a 9-amino acid control peptide consisting of a 'scrambled' 3'5' AVP-binding peptide sequence. Further, polyclonal anti-rat 5'3' AVP-binding peptide antibodies blocked AVP activity, whereas polyclonal anti-bovine 5'3' AVP-binding peptide antibodies had no significant effect. Polyclonal antibodies generated against the 3'5' AVP-binding peptide also blocked AVP activity. These antibodies possibly blocked AVP function by interaction with the lymphocyte AVP receptor, since AVP specifically displaced binding of the antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1990

Onset of secretion of proteins with antiviral activity by pig conceptuses.

In Exp. 1, antiviral activity was detected in Day-15 pregnant uterine flushings (6222 +/- 2167 units/ml) and in conceptus culture medium collected at 0, 1, 2, 4, 8, 16, 24, 32, 40, and 48 h (95, 375, 650, 1216, 1600, 2100, 2017, 2083, 3500 and 5000 units/ml, respectively; R2 = 0.81, P less than 0.01; y = 190.0 + 252.7x - 11.2x2 + 0.2x3. In Exp. 2, antiviral activity of Day-15 conceptus culture medium was reduced 99% after boiling for 20 min (P less than 0.01) and, after 18 h dialysis (6000-8000 Mr cut-off), 100% of the activity was in the retentate. In Exp. 3, antiviral activity was not detected in cultures of conceptuses from Days 10 and 11 and activity was maximal for Day 14 and Day 15 conceptuses (2100 and 2083 units/ml, respectively). Effects of day were best described by a quadratic regression equation (y = 17,652 - 3263x + 150x2; R2 = 0.55, P less than 0.01). In Exp. 4, changes in antiviral activity detected in uterine flushings from pregnant gilts on Days 8, 10, 11, 12, 14 and 15 (1.3, 0, 6.7, 63.3, 580 and 1663 units/ml, respectively) were described by the equation y = -20,743 + 6189x - 606x2 + 20x3 (R2 = 0.85, P less than 0.01). In Exp. 5, low antiviral activities (5-30 units/ml) were detected in all plasma samples collected from the uterine artery and uterine vein of pregnant and cyclic gilts, but values were not significantly influenced by pregnancy status, day or site of collection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Influence of the endometrium, protease inhibitors and freezing on antiviral activity of proteins secreted by pig conceptuses.

In Exp. 1, only medium from cultures containing conceptus tissue had antiviral activity (P less than 0.05). Addition of Day-15 pregnant endometrium or Day-14 cyclic uterine flush proteins to cultures containing 200 mg conceptus tissue decreased antiviral activity (conceptus x endometrial protein interaction, P less than 0.06). Effects of endometrium (-54%) and uterine flush proteins (-40%) on antiviral activity of conceptus cultures did not differ from each other (P greater than 0.10). In Exp. 2, antiviral activity was only detected in cultures containing conceptus tissue (P less than 0.06). The amount of antiviral activity in cultures of Day-15 conceptus tissue was not influenced differently (P greater than 0.10) by culture in medium conditioned by endometrium from Day 10 or Day 12 of pregnancy. However, antiviral activity was undetectable in medium conditioned by endometrium from one of the Day-12 gilts. In Exp. 3, antiviral activity was present in medium from only 1 of 3 cultures from Day-12 gilts when assayed unfrozen. Antiviral activity was lower (P less than 0.01) in cultures of conceptuses from Day 12 than Day 14 of pregnancy; however, antiviral activity increased quadratically (P less than 0.05) when cultures contained 0, 0.01, 0.1 and 1.0 units/ml aprotinin, respectively. Freezing and thawing culture medium did not reduce (P greater than 0.10) antiviral activity compared to medium assayed unfrozen (1438 vs 1354 units/ml, respectively). These results suggest a regulatory influence of the endometrium on secretion of antiviral proteins by pig conceptuses in vitro.

Animals↗
PubMed1989

Differential effects of epidermal growth factor, transforming growth factor-alpha, and vaccinia virus growth factor in the positive regulation of IFN-gamma production.

We have recently shown that epidermal growth factor (EGF) is capable of positive regulation of IFN-gamma production, thus establishing a functional relationship between nonhemopoietic growth factors and the immune system. In order to study this relationship further, EGF and the EGF-related growth factors transforming growth factor-alpha (TGF-alpha) and vaccinia virus growth factor (VGF), which stimulate cellular proliferation via binding to the EGF receptor, were studied for their functional and physicochemical effects on IFN-gamma production. In contrast to the positive signal of purified murine EGF and recombinant human EGF (both at 1 nM), neither synthetic TGF alpha nor recombinant VGF were capable of restoring competence for IFN-gamma production by Th cell-depleted spleen cell cultures. TGF-alpha and VGF, in molar excess, also failed to block the helper signal of EGF for IFN-gamma production. Thus TGF-alpha and VGF failed to functionally compete for the EGF receptor in the murine spleen cell system. Both TGF-alpha and VGF stimulated murine 3T3 cell proliferation at concentrations similar to those of EGF, and thus their failure to provide help for IFN-gamma production was not due to a general lack of biologic activity. Binding studies with 125I-EGF suggest that the EGF receptor on murine lymphocytes is not constitutively expressed, but inducible by the T cell mitogen staphylococcal enterotoxin A. TGF-alpha did not compete with 125I-EGF for the induced receptor. The data suggest that lymphocytes express a novel inducible EGF receptor that differs from that expressed on cells such as 3T3 fibroblasts.

Adjuvants, Immunologic↗
PubMed1988

A novel arginine vasopressin-binding peptide that blocks arginine vasopressin modulation of immune function.

We report on a novel peptide that blocks the neuroendocrine hormone arginine vasopressin (AVP) helper signal for IFN-gamma production by direct interaction with the hormone. The AVP-binding nonapeptide has the sequence Thr-Met-Lys-Val-Leu-Thr-Gly-Ser-Pro (binding peptide). AVP and its 6-amino acid N-terminus cyclic ring pressinoic acid (PA) are both capable of replacing the IL-2 requirement for IFN-gamma production by mouse splenic lymphocytes. We show that the AVP-binding peptide specifically and reversibly blocks AVP help in IFN-gamma production, but fails to block the helper signal of PA. Thus the intact AVP molecule and not just the N-terminal cyclic ring is important for interaction with the binding peptide. AVP interacts with the binding peptide with an apparent KD of approximately 50 nM. The AVP-binding peptide does not inhibit AVP interaction with its receptor on lymphocytes. Interestingly, whereas the AVP-binding peptide does not block the PA helper signal for IFN-gamma induction, the complex of AVP and binding peptide does reversibly block the PA signal. The AVP family of hormones requires conformational flexibility for signal transduction. Thus, we hypothesize that the AVP-binding peptide restricts this flexibility and converts AVP into an antagonist of its own action.

Adjuvants, Immunologic↗
PubMed1988

Antiviral activity of the pregnancy recognition hormone ovine trophoblast protein-1.

Ovine trophoblast protein-1 (oTP-1) is an antiluteolytic protein which plays an important role in maternal recognition of pregnancy. It exhibits a 45-70% amino acid sequence homology with alpha interferons (IFN-alpha s) from various species. We show here that purified oTP-1 has high specific antiviral activity (2-3 X 10(8) units/mg protein) and is thus as potent as any known IFN. oTP-1 is antigenically distinct but does show antigenic relation to both ovine and bovine IFN-alpha s. The antiviral activity of oTP-1 could be demonstrated in Day 12 - Day 16 conceptus culture medium and in allantoic fluid from Day 60 of pregnancy. Our functional and antigenic characterization suggests that oTP-1 is a type of IFN-alpha which performs classic roles associated with IFN-alpha, as well as being the primary conceptus secretory product responsible for maternal recognition of pregnancy.

Allantois↗
PubMed1988

Arginine vasopressin (AVP) replacement of helper cell requirement in IFN-gamma production. Evidence for a novel AVP receptor on mouse lymphocytes.

Arginine vasopressin (AVP), a nine-amino acid neurohypophyseal hormone, is capable of replacing the helper cell requirement for IFN-gamma production by Lyt-2+ mouse splenic lymphocytes. We present data here showing that the AVP helper signal occurs via interaction with a novel R on splenic lymphocytes and involves primarily the N-terminal six-amino acid cyclic ring (pressinoic acid) with the C-terminal three-amino acid end of AVP playing a minor role. Pressinoic acid was capable of providing help at concentrations similar to those of AVP, whereas oxytocin and isoleucine pressinoic acid were 10- and 100-fold less effective, respectively. Isoleucine pressinoic acid has the same structure as pressinoic acid except for the substitution of isoleucine for phenylalanine in position 3 of the sequence. Consistent with the function data, R binding competitions with splenic lymphocyte membrane preparations showed that AVP and pressinoic acid competed similarly with [3H]AVP, whereas oxytocin and isoleucine pressinoic acid were much less effective competitors. Further characterization of the AVP lymphocyte R was performed using AVP analogues having well defined agonist and antagonist activities on either V1 (vasopressor) R or V2 (antidiuretic) R. The AVP helper signal was blocked by the V1 antagonist [d(CH2)1(5) Tyr(methyl)]AVP but not by another V1 antagonist, [d(CH2)1(5)D-Tyr(ethyl)2Val4]AVP. Both V1-R antagonists were able to block [3H]AVP binding to the V1-R on liver cells, whereas only the V1 antagonist that blocked AVP help was able to compete effectively for the spleen AVP-R. Neither a V2 agonist nor a V2 antagonist had any effect on AVP help in IFN-gamma production. These data strongly indicate the presence of a novel AVP-R on spleen lymphocytes, which is related to the classic V1-R on liver cell membranes.

Adjuvants, Immunologic↗
PubMed1988

Use of synthetic peptides to identify an N-terminal epitope on mouse gamma interferon that may be involved in function.

We previously have assigned N-terminal specificity to three hamster monoclonal antibodies (mAbs I, II, and III) produced to mouse recombinant gamma interferon (IFN-gamma), based on the ability of the N-terminal peptide IFN-gamma-(1-39) to block binding of 125I-labeled IFN-gamma (125I-IFN-gamma) and on the ability of these antibodies to bind 125I-IFN-gamma-(1-39). Only mAb I blocked function and binding to the IFN-gamma receptor, suggesting that it may bind to a region of the molecule involved in interaction with the receptor. To further define the epitope specificities of the antibodies, a series of N-terminal peptides were synthesized and tested for their ability to block antibody binding of 125I-IFN-gamma. Peptides IFN-gamma-(1-39), IFN-gamma-(1-20), IFN-gamma-(3-20), and IFN-gamma-(5-20) inhibited binding of 125I-IFN-gamma by mAb I in order of decreasing effectiveness, while peptide IFN-gamma-(7-20) was without effect. Peptides IFN-gamma-(1-39), IFN-gamma-(1-20), and IFN-gamma-(3-20) also inhibited binding of 125I-IFN-gamma by mAb II but were less effective when compared with their inhibition of mAb I. IFN-gamma-(5-20) and IFN-gamma-(7-20) did not inhibit binding by mAb II. Peptides IFN-gamma-(1-10), IFN-gamma-(10-30), and IFN-gamma-(21-44) did not inhibit either mAb I or mAb II. While IFN-gamma-(1-39) and IFN-gamma-(10-30) inhibited binding by mAb III, neither IFN-gamma-(1-20) nor any of its truncated forms were inhibitory. All three antibodies had similar Kd values for 125I-IFN-gamma. A prediction of the secondary structure of the molecule and the peptide inhibition data suggest that the epitope (possible receptor binding region) for mAb I involves a loop in the area containing residues 12-20, with sequences N-terminal to these residues possibly stabilizing the loop conformation. Direct evidence that the N-terminal 1-39 region of IFN-gamma is important in receptor binding was the observation that IFN-gamma-(1-39), but not the C-terminal IFN-gamma-(95-133), competed with 125I-IFN-gamma for the receptor on mouse L cells. IFN-gamma-(1-39) also specifically blocked IFN-gamma antiviral activity at concentrations that blocked binding to the receptor. The fact that IFN-gamma-(1-39) was the only peptide that blocked both IFN-gamma binding to receptor and function is consistent with the antibody competition data, where it was the most effective peptide in blocking binding of 125I-IFN-gamma by the N-terminal-specific mAbs. The combination of peptide mapping of epitope specificities and receptor competition should further help define the structural basis for IFN-gamma action.

Animals↗
PubMed1988

Steric relationship of amino-terminal and carboxy-terminal domains of murine interferon-gamma as assessed by monoclonal antibodies.

Spleen cells from a hamster immunized with murine interferon-gamma (IFN-gamma) carboxy-terminal (95-133) synthetic peptide [IFN-gamma (95-133)] conjugated to keyhole limpet hemocyanin (KLH) were fused with mouse myeloma cells, resulting in the production of an anti-IFN-gamma (95-133) monoclonal antibody, which reacted with IFN-gamma. This monoclonal antibody bound [125I]IFN-gamma in a dose-dependent and reversible fashion, and neutralized the antiviral and macrophage priming activities of IFN-gamma. Antibody-antibody competition for [125I]IFN-gamma binding, using this carboxy-terminal-specific antibody and two previously described amino-terminal-specific monoclonal antibodies, indicated that the carboxy-terminal-specific monoclonal antibody competed only with itself and that the two amino-terminal-specific monoclonal antibodies similarly competed only with each other for [125I]IFN-gamma. The data suggest that the amino- and carboxy-terminal IFN-gamma domains important for function are sterically distant from one another, and suggest the intriguing possibility that interaction of IFN-gamma with its receptor may involve more than one binding site on the IFN-gamma molecule.

Animals↗
PubMed1987

Phospholipase A2 treatment of lymphocytes provides helper signal for interferon-gamma induction. Evidence for second messenger role of endogenous arachidonic acid.

To examine the role of endogenous arachidonic acid (AA) as the possible second messenger signal in interferon-gamma (IFN-gamma) production, helper cell-depleted mouse spleen cell cultures were treated with the enzyme phospholipase A2 (PLA2). Treatment with PLA2 from several different animal sources at concentrations between 10 and 300 U/ml resulted in complete, dose-dependent restoration of competence for IFN-gamma production. By comparison, phospholipase C (PLC) from several different species failed to restore competence at concentrations between 0.3 and 30 U/ml; the inability of PLC to provide the helper signal for induction of IFN-gamma was not due to cytotoxicity. Since PLA2 provides competence for IFN-gamma production by sn-2 hydrolysis, it was of interest to identify eicosanoids and other lipids released from [3H]-AA labeled cells by PLA2 and PLC. Treatment of spleen cells with PLA2, but not PLC, resulted in the appreciable release of AA only. Sufficient AA was released from spleen cells for restoration of competence for production of IFN-gamma. All glycerol-derived cell membrane phospholipids examined (phosphatidylethanolamine, -inositol, -choline, and -serine) incorporated labeled AA which was releasable by treatment with PLA2. The data support and extend previous studies which suggested that AA plays a pivotal role in mediation of the interleukin 2 helper signal for IFN-gamma production.

Animals↗
PubMed1986

Epitope and functional specificity of monoclonal antibodies to mouse interferon-gamma: the synthetic peptide approach.

Spleen cells from hamsters immunized with recombinant mouse interferon-gamma (IFN-gamma) were fused with mouse myeloma cells, resulting in the production of four anti-IFN-gamma monoclonal antibodies. Binding of 125I-IFN-gamma by these protein A-bound antibodies was specifically blocked by cold IFN-gamma. Binding by three of these antibodies was also blocked by a synthetic peptide corresponding to the N-terminal 1-39 amino acids of IFN-gamma, whereas a corresponding C-terminal (95-133) peptide had no effect on binding. The N-terminal specificity of these three antibodies was confirmed by their specific binding of 125I-N-terminal (1-39) peptide. One of the N-terminal specific monoclonal antibodies inhibited both antiviral and macrophage priming (for tumor cell killing) activities of IFN-gamma, whereas the other two had no effect on either biologic function. The selectivity of the inhibition of IFN-gamma function was not due to a differential ability of the N-terminal specific antibodies to bind IFN-gamma. Blocking experiments with cold IFN-gamma and N-terminal peptide suggest that the epitope specificities of the monoclonal antibodies could be determined by the conformational or topographic structure of IFN-gamma. An exact determination of the epitope specificity of the monoclonal antibody that inhibited IFN-gamma function could provide insight into the structural basis for the role of the N-terminal domain in the biologic function of IFN-gamma. Polyclonal antibodies to either the N-terminal or the C-terminal peptides also inhibited both the antiviral and the macrophage-priming activities of IFN-gamma. All of the antibodies that inhibited IFN-gamma function also blocked binding of IFN-gamma to membrane receptor on cells, whereas antibodies that did not block function also did not inhibit binding. The data suggest that both the N-terminal and the C-terminal domains of IFN-gamma play an important role in its antiviral and macrophage-priming functions, possibly in a cooperative manner.

Amino Acid Sequence↗
PubMed1985

Lipopolysaccharide and polyribonucleotide activation of macrophages: implications for a natural triggering signal in tumor cell killing.

There is evidence that activation of macrophages for tumor cell killing can involve either two signals (interferon/lipopolysaccharide, for example) or one signal (lipopolysaccharide or double-stranded RNA, for example). We investigated the apparent one-signal activation of bone marrow-derived macrophages for P815 mastocytoma killing by treatment with lipopolysaccharide (LPS) or by the synthetic double-stranded polyribonucleotide polyinosinic acid-polycytidylic acid (poly I:C). We found that "direct" activation of macrophages by either LPS or poly I:C was still a two-signal process. Based on antibody neutralizations, the first signal was probably mediated by LPS or poly I:C induced alpha/beta interferon in the macrophage cultures, and the second signal was that of a direct effect of the LPS or poly I:C on the cell. The fact that poly I:C can provide the triggering signal for macrophage activation suggests a possible role for double-stranded RNA structures in macrophage triggering. Such double-stranded RNA requirements could be met by single-stranded RNAs that possess significant double-strandedness in their structures.

Animals↗
PubMed1985

Mechanism of calcium ionophore A23187-induced priming of bone marrow-derived macrophages for tumor cell killing: relationship to priming by interferon.

Interferon primes macrophages for tumor cell killing by rendering them sensitive to triggering agents such as lipopolysaccharide. In an attempt to determine the nature of the priming signal, we tested phorbol 12-myristate 13-acetate, diacylglycerol, platelet-activating factor, arachidonic acid, leukotriene B4, and the calcium ionophore A23187 for their ability to prime mouse bone marrow-derived macrophages for activation to kill P815 mastocytoma target cells. The ionophore A23187 was the only substance that was able to replace the interferon priming signal. A23187 priming appeared to be due in part to induction of interferon alpha/beta in the macrophage cultures, since its effect was partially but specifically blocked by antibody to interferon alpha/beta. Consistent with this was the observation that A23187 induced interferon alpha/beta production in macrophage cultures. The fact that A23187 priming was not completely reversed by antibody to interferon would suggest that factors unrelated to interferon induction also played a role in macrophage priming. The failure of phorbol myristate acetate or diacylglycerol to prime macrophages for tumor cell killing would suggest that activation of protein kinase C is not sufficient for priming. Thus, A23187 appears to provide the priming signal for macrophage killing through the combination of interferon- and non-interferon-induced mechanisms.

Animals↗
PubMed1985

Interleukin 2-mediated events in gamma-interferon production are calcium dependent at more than one site.

Both leukotrienes and dibutyryl cyclic GMP can replace the interleukin 2 (IL 2) requirement for gamma-interferon (gamma-IFN) production. In this study, the Ca dependence of the IL 2 help was demonstrated by blockage of gamma-IFN production by the Ca blocker Mn, and the competitive reversal of this block by Ca. Neither leukotriene C4 nor dibutyryl cyclic GMP could reverse the Mn block, which suggests that arachidonic acid release from phospholipids is not the only Ca-dependent event in IL 2 help for gamma-IFN production. A role for calmodulin or protein kinase C in the IL 2-mediated events was suggested by the blockage of gamma-IFN production by chlorpromazine. Relatively high concentrations of Ca were able to replace the IL 2 helper effects. Consistent with this were Ca influx experiments that showed that IL 2 helper signals for gamma-IFN production involved activation of a Ca channel.

Animals↗