Search PubMed⌕ Search

Biomedical subjects

B A Torres

Publications and source records attributed to B A Torres.

At least 37 records · Page 2Linked to original sources
PubMed1996

Characterization of Nef-induced CD4 T cell proliferation.

Studies on Nef, a regulatory protein encoded by human immunodeficiency virus (HIV), suggest it plays an important role in HIV pathogenesis. Previously, we reported that Nef binds to class II MHC antigens and induces proliferation of human peripheral blood mononuclear cells (PBMC). Herein, we further characterize PBMC responses to Nef. Polyclonal antisera generated against Nef synthetic peptides blocked proliferation. Responses were T cell-specific and required antigen-presenting cells (APC). T cells responded in the presence of paraformaldehyde-inactivated APC, suggesting that Nef is presented in an unprocessed form. Nef-stimulated cells produced IL 2 and IFN gamma, products of T helper-1 cells. Thus, Nef has superantigen properties in that it binds to MHC class II antigens, does not need processing to be presented by APC, and activates T cells, causing proliferation and production of the T helper 1 cytokines, IL 2 and IFN gamma. The identification of an HIV protein that activates T cells is of considerable interest, given that HIV replicates in T cell blasts but not in quiescent cells.

Adult↗
PubMed1996

A multicenter randomized, masked comparison trial of natural versus synthetic surfactant for the treatment of respiratory distress syndrome.

OBJECTIVE: To compare the efficacy and safety of two surfactant preparations in the treatment of respiratory distress syndrome (RDS). METHODS: We conducted a randomized, masked comparison trial at 21 centers. Infants with RDS who were undergoing mechanical ventilation were eligible for treatment with two doses of either a synthetic (Exosurf) or natural (Infasurf) surfactant if the ratio of arterial to alveolar partial pressure of oxygen was less than or equal to 0.22. Crossover treatment was allowed within 96 hours of age if severe respiratory failure (defined as two consecutive arterial/alveolar oxygen tension ratios < or = 0.10) persisted after two doses of the randomly assigned surfactant. Four primary outcome measures of efficacy (the incidence of pulmonary air leak (< or = 7 days); the severity of RDS; the incidence of death from RDS; and the incidence of survival without bronchopulmonary dysplasia (BPD) at 28 days after birth) were compared by means of linear regression techniques. RESULTS: The primary analysis of efficacy was performed in 1033 eligible infants and an analysis of safety outcomes in the 1126 infants who received study surfactant. Preentry demographic characteristics and respiratory status were similar for the two treatment groups, except for a small but significant difference in mean gestational age (0.5 week) that favored the infasurf treatment group. Pulmonary air leak (< or = 7 days) occurred in 21% of Exosurf- and 11% of infasurf-treated infants (adjusted relative risk, 0.53; 95% confidence interval, 0.40 to 0.71; p < or = 0.0001). During the 72 hours after the initial surfactant treatment, the average fraction of inspired oxygen (+/-SEM) was 0.47 +/- 0.01 for Exosurf- and 0.39 +/- 0.01 for infasurf-treated infants (difference, 0.08; 95% confidence interval, 0.06 to 0.10; p < 0.0001); the average mean airway pressure (+/-SEM) was 8.6 +/- 0.1 cm H2O; for Exosurf- and 7.2 +/- 0.1 cm H2O for Infasurf-treated infants (difference, 1.4 cm H2O; 95% confidence interval, 1.0 to 1.8 cm H2O; p < 0.0001). The incidences of RDS-related death, total respiratory death, death to discharge, and survival without bronchopulmonary dysplasia at 28 days after birth did not differ. The number of days of more than 30% inspired oxygen and of assisted ventilation, but not the duration of hospitalization, were significantly lower in Infasurf-treated infants. CONCLUSION: Compared with Exosurf, Infasurf provided more effective therapy for RDS as assessed by significant reductions in the severity of respiratory disease and in the incidence of air leak complications.

Bronchopulmonary Dysplasia↗
PubMed1996

Structural requirements for agonist activity of a murine interferon-gamma peptide.

We have demonstrated previously that murine interferon-gamma (MuIFN-gamma) binds to the extracellular domain of the receptor alpha chain through its N-terminus and subsequently to the cytoplasmic domain of the receptor via its C-terminus. Binding of the C-terminus to the cytoplasmic domain of the receptor is thought to occur following endocytosis of the IFN-gamma-receptor complex. In fact, the MuIFN-gamma C-terminus peptide, MuIFN-gamma (95-133), has full agonist activity on macrophages where it is internalized through pinocytosis. Here we examine the structural elements required for the agonist activity of MuIFN-gamma (95-133). Disruption of the alpha helical structure of the peptide by proline substitutions or truncation of the helix resulted in significant loss of binding or loss of antiviral activity or both and induction of MHC class II molecules. Further, removal of the polycationic sequence RKRKR in the tail beyond the helical structure also resulted in loss of agonist activity. Thus, we have isolated the functional site on MuIFN-gamma to the C-terminus and have shown that its helical structure and polycationic tail are required for binding to the cytoplasmic domain of the receptor and induction of biologic activity.

Adjuvants, Immunologic↗
PubMed1996

Superantigens: structure and relevance to human disease.

Superantigens are a class of immunostimulatory molecules produced by bacteria and viruses. Their potent immune effects are due to their unique ability to bind to the major histocompatibility complex (MHC) outside the antigen-binding cleft and to stimulate T cells in a T-cell receptor (TCR) Vbeta-specific manner. Structural studies have revealed the binding sites involved in the MHC/superantigen/TCR complex. The bacterial superantigens are responsible for a number of syndromes, including food poisoning and toxic shock syndrome, but their effects may be not only acute but also chronic and complex. Recent evidence suggests that superantigens may be relevant to the pathogenesis of autoimmune and immunodeficiency disorders. To illustrate the detrimental effects of superantigens on disease outcome, evidence demonstrating the modulation of experimental allergic encephalomyelitis, an animal model for multiple sclerosis, by superantigen, as well as the potential role of superantigens in HIV pathogenesis of AIDS, will be presented. The information presented may provide valuable insight into the role of superantigens in autoimmunity and HIV infection.

Animals↗
PubMed1994

Identification of an HIV-1 Nef peptide that binds to HLA class II antigens.

Overlapping peptides corresponding to the entire Nef (HIVBRU) sequence were tested for their relative abilities to block binding of staphylococcal enterotoxins (SEs) to Raji cells. An internal sequence, Nef(123-160), blocked binding of two highly homologous SEs, SEA and SEE, while it was less effective against SEB and SEC1. Nef(123-160) bound directly class II DR antigens, as assessed by specific antibodies, and its binding was significantly inhibited by SEE, and also by SEA to a lesser degree. Purified Nef inhibited specific binding of SEA to Raji cells in a dose-dependent manner. Nef induced IL 2 production and proliferation by human mononuclear cells. Definitive expansion of specific V beta T cell populations was not observed, possibly due to lesser mitogenic activity of Nef relative to SEs. Thus, Nef may have mitogenic activity similar to that of superantigens.

Amino Acid Sequence↗
PubMed1994

Complementary peptides as probes to explore neuropeptide receptors on lymphocytes.

Studies on neuroendocrine hormone receptor have been hampered by low numbers and concentrations of receptors found within and outside the neuroendocrine system. The complementary peptide approach is particularly useful for dealing with this problem and has been used to characterize lymphoid receptors for arginine vasopressin (AVP), corticotropin (ACTH), substance P, and opioid peptides. A nonapeptide derived by reading of the complementary DNA strand of the bovine AVP gene in the 3' to 5' direction specifically blocks the AVP helper signal for interferon-gamma production by mouse T lymphocytes. Antibodies to 3'-5' AVP-binding peptide bound to cells, and the binding was inhibited by excess AVP. Thus, binding of anti-3'-5'AVP-binding peptide antibodies to the AVP receptor was specific. The complementary peptide approach has also been used to produce antibodies specific for the ACTH receptor complex. Complementary peptides to ACTH derived by reading in either the 5' to 3' or 3' to 5' direction were able to bind to ACTH. Monospecific antibodies to the ACTH (1-24) complementary peptide caused an ACTH-like steroidogenic response of cultured mouse adrenal cells, presumably by binding to the ACTH receptor, and binding was specifically inhibited by ACTH. The ACTH receptor complex from solubilized adrenal cells was shown to consist of four subunits with M(r) 83,000, 64,000, 52,000, and 22,000. The 83,000 and 52,000 M(r) subunits are disulfide linked and noncovalently associated with the other subunits, with binding of labeled ACTH localized to the 83,000 M(r) subunit. Similarly, a complementary peptide was shown to bind directly to substance P in a saturable and dose-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Application of the constant exposure time technique to transformation experiments with fission neutrons: failure to demonstrate dose-rate dependence.

A direct comparison of the effectiveness of fission neutrons at high (11.0-31.3 cGy/min) or several low dose-rates (0.14-3.2 cGy/min) was carried out under identical conditions. Monolayers of exponentially growing C3H/10T1/2 cells were exposed at 37 degrees C to reactor-produced neutrons (fluence-mean energy En = 0.68 MeV, < or = 5% gamma component, frequency mean linear energy yF = 21 keV/micron, dose mean lineal energy yD = 42 keV/micron in an 8-micron spherical cavity). Survival or transformation induction were studied at five doses from 10.5 to 94 cGy. In low dose-rate irradiations, these doses were protracted over 0.5, 1, 3 or 4.5 h, resulting in 17 different dose-rates. Up to six experiments were performed at each of five exposure times. Concurrently with transformation we studied cell proliferation in control versus cells irradiated at 40 cGy (acute and a 4.5-h protraction) and found no evidence of a shift in the cell cycle distribution among these cells. At a given dose and dose-rate, the effect of dose protraction on survival or transformation was assessed by the dose-rate modifying factor (DRMF), defined as the low:high dose-rate effect ratio at the same dose. Survival or transformation induction curves were nearly linear with initial slopes, respectively, of about 6.5 x 10(-3) or 6.2 x 10(-6) cGy-1. Consistent with dose-response curves, DRMFs were independent of the dose and dose-rate. The mean values of the DRMF with their uncertainties and 99% confidence intervals, based on measurements in individual doses and dose-rates for survival or transformation were, respectively: 1.01 +/- 0.03 (0.92, 1.09) or 0.98 +/- 0.04 (0.83, 1.08) indicating a similar precision in determining DRMF for survival or transformation, and no dose or dose-rate influence on these end points.

Animals↗
PubMed1993

Bacterial and retroviral superantigens share a common binding region on class II MHC antigens.

Staphylococcal enterotoxin A (SEA), one of the most potent T-cell mitogens known, has been classified as a bacterial superantigen on the basis of ability to stimulate V beta-specific T-cell subsets. SEA interacts with class II major histocompatibility complex (MHC) antigens on antigen-presenting cells and the T-cell antigen receptor (TCR) on T cells, resulting in a ternary complex of MHC-SEA-TCR. Mls antigens are known to be products of mouse mammary tumour virus (MMTV), and it has been reported that two exogenous strains of MMTV encode retroviral superantigens in the open reading frames of the 3' long terminal repeat of the viral genome; however, no binding of the putative MMTV superantigen to either MHC antigens or TCR has been demonstrated. Here we use synthetic peptides to identify a site on the MMTV-1 superantigen that binds to class II MHC antigens. The site is encompassed by amino-acid residues 76-119 of the MMTV-1 superantigen. Direct binding and competition experiments show that the MMTV superantigen and SEA bind to at least one common region on class II MHC antigens.

Amino Acid Sequence↗
PubMed1993

Passive antibody protection of cats against feline immunodeficiency virus infection.

All six cats passively immunized with sera from either feline immunodeficiency virus (FIV)-vaccinated cats or cats infected with FIV (Petaluma strain) were protected from homologous FIV infection at a challenge dose that infected all six control cats. Passive immunization with sera from cats vaccinated with uninfected allogeneic T cells used to grow the vaccine virus did not protect either of two cats against the same FIV challenge. These results suggest that antiviral humoral immunity, perhaps in synergy with anticellular antibodies, may be responsible for previously reported vaccine protection.

Animals↗
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↗