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Biomedical subjects

J Rivera

Publications and source records attributed to J Rivera.

At least 181 records · Page 10Linked to original sources

Quantitative determination of adenovirus-mediated gene delivery to rat cardiac myocytes in vitro and in vivo.

To optimize the use of modified adenoviruses as vectors for gene delivery to the myocardium, we have characterized infection of cultured fetal and adult rat cardiac myocytes in vitro and of adult cardiac myocytes in vivo by using a replication-defective adenovirus carrying the chloramphenicol acetyltransferase (CAT) reporter gene driven by the cytomegalovirus promoter (AdCMVCATgD). In vitro, virtually all fetal or adult cardiocytes express the CAT gene when infected with 1 plaque-forming unit of virus per cell. CAT enzymatic activity can be detected in these cells as early as 4 hr after infection, reaching near-maximal levels at 48 hr. In fetal cells, CAT expression was maintained without a loss in activity for at least 1 week. Using in vitro studies as a guide, we introduced the AdCMVCATgD virus directly into adult rat myocardium and compared the expression results obtained from virus injection with those obtained by direct injection of pAdCMVCATgD plasmid DNA. The amount of CAT activity resulting from adenovirus infection of the myocardium was orders of magnitude higher than that seen from DNA injection and was proportional to the amount of input virus. Immunostaining for CAT protein in cardiac tissue sections following adenovirus injection demonstrated large numbers of positive cells, reaching nearly 100% of the myocytes in many regions of the heart. Expression of genes introduced by adenovirus peaked at 5 days but was still detectable 55 days following infection. Adenoviruses are therefore a very useful tool for high-efficiency gene transfer into the cardiovascular system.

Animals↗

Environmental analysis of polychlorinated terphenyls: distribution in shellfish from the Ebro Delta (Mediterranean).

Polychlorinated terphenyls (PCTs) have characteristics almost identical with those of polychlorinated biphenyls (PCBs) and have been used for analogous applications, but only sporadic reports of the occurrence of PCTs in the environment have been published. High-resolution gas chromatography with electron-capture detection (HRGC-ECD) and mass spectrometric detection in the selected ion monitoring mode was used to analyse samples for PCTs. The homologue distribution of Aroclor 5432, 5460, Leromoll 141 and the PCTs in samples of shellfish from the Ebro Delta (Catalonia, Spain) was established, taking into account the contribution of the [M-Cl2]+ fragments. Quantification was achieved by HRGC-ECD. Concentrations were between 790 and 3 ng/g (dry mass).

Animals↗

Repeated infusions of DDAVP induce low response of FVIII and vWF but not of plasminogen activators.

Although the vasopressin analogue desamino-d-arginine vasopressin (DDAVP) induces a very well characterized increase in factor VIII (FVIII), von Willebrand factor (vWF), tissue plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA), the mechanism(s) by which DDAVP enhances the plasma levels of these proteins is poorly understood. Some clinical evidence suggests that certain patients repeatedly treated with DDAVP at closely spaced intervals become progressively unresponsive (tachyphylaxis). In order to investigate the effect of repeated DDAVP infusion on the behaviour of FVIII, vWF, t-PA and u-PA, we infused three different doses of DDAVP (0.3 microgram/Kg) to six healthy volunteers (19-26 years old, mean 22) at 12-hour intervals. Blood samples were collected immediately before and after DDAVP. The second and third infusion of DDAVP induced a low response of FVIII and vWF. In contrast, t-PA and u-PA exhibited a consistent response after each DDAVP infusion. If the progressive decrease of FVIII and vFW response observed in healthy subjects after repeated doses of DDAVP at 12-hour intervals is extended to haemophiliacs and von Willebrand's patients, the usefulness of desmopressin may be limited when these proteins must be raised therapeutically for a prolonged period of time. Finally, our results suggest that the mechanism for regulating the release of vWF and plasminogen activators in the conditions of our study are not dependent.

Adult↗

Evaluation of shipboard formation of a neurotoxicant (trimethylolpropane phosphate) from thermal decomposition of synthetic aircraft engine lubricant.

MIL-L-23699 lubricants that are composed principally of trimethylolpropane triheptanoate (TMP) and tricresyl phosphate (TCP) have been shown to form a neurotoxicant, trimethylolpropane phosphate (TMPP), during pyrolysis and/or combustion. Mechanistically, TMPP is thought to irreversibly inhibit the GABA-mediated inhibitory response and thereby produce epileptiform clonic/tonic seizures with convulsions followed by death. Thermal decomposition of MIL-L-23699 lubricant produces TMPP under laboratory conditions, but this product has not been detected in the workplace following actual fires. This study has examined whether TMPP is produced during an actual shipboard fire by placing the synthetic lubricant in a fire environment aboard the ex-U.S.S. Shadwell, Mobile, Alabama. Both biological and chemical analyses were performed on the thermally decomposed lubricant to ensure detection of the neurotoxic material. Under the conditions of this study, the formation of TMPP during a shipboard fire was confirmed. The implications of this finding for safe management of post-fire cleanup are discussed.

Bridged Bicyclo Compounds, Heterocyclic↗

Total parenteral nutrition containing medium- vs. long-chain triglyceride emulsions elevates plasma cholesterol concentrations in rats.

Male Fischer 344 rats (235-246 g) were fed for 6-14 d by intravenous or intragastric infusion with total parenteral nutrition (TPN) solutions providing 40 or 65% of nonprotein energy as fat from long-chain triglyceride (LCT) or a 3:1 admixture of medium-chain triglyceride (MCT) and LCT emulsions. In three separate experiments, plasma cholesterol concentrations were significantly greater (24-32%) with intravenous infusion of TPN solutions containing MCT-LCT rather than LCT. Plasma cholesterol concentrations in rats were not significantly different with intragastric infusion of TPN solutions containing MCT-LCT rather than LCT. Hepatic total lipid and triglyceride concentrations were not significantly different. Hepatic total cholesterol and esterified cholesterol concentrations were significantly lower in animals given 65% of energy from MCT-LCT rather than LCT emulsions (main effects, two-way ANOVA). The concentration of individual hepatic acyl-CoA esters reflected the fatty acid profiles of the lipid emulsions infused. Total hepatic acyl-CoA concentrations suggested differences in utilization of acyl-CoA esters with intravenous infusion of MCT-LCT rather than LCT and were consistent with rapid oxidation of MCT. These data demonstrate that MCT-LCT elevates plasma cholesterol concentrations compared with LCT emulsions with intravenous, but not with intragastric, infusion of TPN solutions in rats.

3-Hydroxybutyric Acid↗

Immunity and responses of circulating leukocytes and lymphocytes in monkeys to aerosolized staphylococcal enterotoxin B.

Rhesus monkeys immunized intramuscularly or orally with staphylococcal enterotoxin B (SEB) toxoid or SEB toxoid incorporated in microspheres made of poly(DL-lactide-co-glycolide) were challenged with a lethal dose of aerosolized SEB to study their immunity and cellular responses in the circulation. It was found that circulating antibodies play a critical role in preventing SEB from triggering toxicosis. Monkeys with high levels of antibodies survived, while those with low levels underwent 2 to 3 days of toxicosis and died. Intramuscular immunization induced high levels and oral immunization induced low levels of antibodies. The circulating antibodies in surviving monkeys decreased dramatically within 20 min and started to rebound at 90 min after SEB challenge. At 90 min, the dying monkeys showed in the circulation a dramatic increase of polymorphonuclear leukocytes and decreases of NK cells and monocytes (CD16 and CD56 markers) as well as of lymphocytes with HLA-DR, CD2, CD8, and IL2R alpha (CD25) markers. The number of polymorphonuclear leukocytes showed an inverse correlation with the numbers of monocytes and various lymphocyte subpopulations which, except for IL-2R, CD16, and CD56(+) cells, showed a direct correlation with one another. The changes in the populations of leukocytes, monocytes, NK cells, and lymphocytes seem to be an indication of initial toxicosis; however, the roles of these cells in toxicosis and death remain to be defined.

Aerosols↗

Early supplementary feeding and cognition: effects over two decades.

The study reported in this Monograph of the effects of early supplementary feeding on cognition included two data collection periods: a longitudinal investigation spanning the years 1969-1977 and a cross-sectional follow-up carried out in 1988-1989. The study was conducted in four rural villages in Guatemala and compared the differential effects of exposure in childhood (0-7 years) to an Atole supplement (11.5 g of protein; 163 kcal) or a Fresco supplement (59 kcal) on performance on a battery of psychoeducational and information-processing tests in adolescence and young adulthood (11-24 years). In this report, particular attention is given to a cohort of subjects who were exposed to the supplement prenatally and during at least the first 2 years of postnatal life. Data on this subsample are contrasted with those on a cohort of subjects who received the supplement only after 24 months of life. The Monograph also reports results from an analysis of the supplementation effects in infancy and early childhood. Consistent differences between groups on the psychoeducational tests were observed. Adolescents from Atole villages scored significantly higher on tests of knowledge, numeracy, reading, and vocabulary than Fresco subjects. Atole was also associated with a faster reaction time in information-processing tasks. Significant interactions helped identify two groups who benefited more from the Atole treatment: those at the lowest levels of socioeconomic status and those who attained the highest levels of primary schooling. The consistent differences in test performance established in the follow-up assessment contrast sharply with the few and less pronounced between-group differences observed in the infancy and preschool periods. After close scrutiny of alternative hypotheses, it is concluded that nutritional differences provide the strongest explanation for the test performance differences observed in the follow-up between the subjects exposed to the Atole and those exposed to the Fresco supplement.

Adolescent↗

Diarrhea and growth among children under 18 months of age in Rio de Janeiro.

A study conducted in a periurban Rio de Janeiro community, Vila do João, sought to assess the extent to which diarrhea was influencing the growth of infants and young children. Using a prospective research design, the investigators studied a population of 159 children under 18 months of age living in the study area during the period January--September 1985. Weight and length measurements were used to calculate monthly weight and length increases. Information on diarrhea morbidity was collected at seven-day intervals by means of house-to-house visits. A multiple linear regression model was used to carry out the statistical analysis, which showed inverse and statistically significant correlations between the prevalence of diarrhea and increases in weight and length. It was estimated that the presence of diarrhea reduced increases in weight and length. It was estimated that the presence of diarrhea reduced increases in weight and length by averages of 13.4 g and 0.132 mm per day. These findings support the idea that control of diarrhea can improve nutritional status among children in developing countries.

Age Factors↗

Interaction of aggregated native and mutant IgE receptors with the cellular skeleton.

When aggregated, cell surface proteins become resistant to solubilization by detergents, presumably because of aggregation-induced or -stabilized interactions between the membrane protein and the cytoskeleton or plasma membrane skeleton. We genetically engineered variants of the tetrameric high-affinity receptor for IgE (Fc epsilon RI) to identify a site on its alpha, beta, or gamma chains that mediates such putative interactions. Using flow cytofluorometry, we studied rat basophilic leukemia cells, transiently transfected COS cells, and stably transfected P815 cells bearing wild-type and mutated receptors. We observed that (i) solubilization was markedly dependent on the degree of aggregation, the extent varying somewhat with the cell type and, particularly at lower levels of aggregation, with the time after addition of detergent; (ii) truncation of no single cytoplasmic domain of the alpha, beta, or gamma chains ablated the insolubilization effect; and (iii) incomplete receptors were also efficiently insolubilized by aggregation. Thus receptors consisting only of alpha and gamma chains, a "receptor" consisting of only the ectodomain of the alpha chain attached to the plasma membrane by a glycosyl-phosphatidyl inositol anchor, and "receptors" consisting only of minimally modified gamma chains were resistant to solubilization after aggregation. We conclude that no unique subunit or domain of Fc epsilon RI mediates the insolubilization phenomenon. Our results support a model in which the bridging of membrane proteins leads to their becoming nonspecifically enmeshed in a network of membrane skeletal proteins on either the outside and/or the inside of the membrane so that dissolution of the lipid bilayer becomes irrelevant.

Animals↗

Energy expenditure in rats maintained with intravenous or intragastric infusion of total parenteral nutrition solutions containing medium- or long-chain triglyceride emulsions.

Energy expenditure was determined in male Fischer 344 rats (235-246 g) fed by intravenous (IV) or intragastric (IG) infusion with total parenteral nutrition solutions providing 65% of nonprotein energy as fat from long-chain triglyceride (LCT) or a 3:1 admixture of medium-chain triglyceride (MCT) and LCT emulsions. Respiratory gas exchange and somatomotor activity were assessed continuously for 24 h during d 5 and 11 of infusion feeding. The MCT infusion resulted in one-third the weight gain noted with LCT infusion (MCT, 10 +/- 2 g/14 d; LCT, 32 +/- 4 g/14 d; P less than 0.0001). Insulin concentration was 60% higher with IV than with IG infusion and approximately 100% higher with IV-MCT than with IG-MCT or LCT infusion (P less than 0.05). Rats receiving IV infusion of MCT displayed similar levels of motor activity but 8-13% greater daily energy expenditure (kJ.kg-0.75.kJ intake-1) than rats receiving IG-MCT or LCT infusion (P less than 0.05). The MCT infusion also resulted in an elevation in respiratory quotient after cessation of nutrient infusion (MCT, 0.87-0.92; LCT, 0.83-0.85; P less than 0.05). Total and resting energy expenditure decreased approximately 13% from 5 to 11 d of infusion feeding. The lower weight gain and greater energy expenditure seen with MCT- compared with LCT-supplemented total parenteral nutrition may be mediated by higher insulin concentrations.

Animals↗

Effects of staphylococcal enterotoxin B on rodent mast cells.

Staphylococcal enterotoxin B (SEB) was tested in rodent mast cell cultures for the release of serotonin. Both rat RBL-2H3 mast cells and murine peritoneal cells released serotonin after SEB stimulation in culture. Release of serotonin in RBL-2H3 cells depended on the concentration of SEB; an appreciable release was seen at 50 micrograms/ml. The release of serotonin was not due to cell death. Serotonin release could be enhanced by bradykinin but not by vasoactive intestinal peptide, substance P, lipopolysaccharide from Salmonella typhimurium, the calcium ionophore A23187, acetylcholine, adenosine, 5-hydroxyeicosatetraenoic acid, indomethacin, or phorbol myristate acetate. SEB bound directly to the membrane of RBL-2H3 mast cells, and the SEB-binding site, the presumptive receptor, appeared to be a protein. The SEB receptor could not be capped under membrane-capping conditions, and serotonin release could not be enhanced by attempts to cross-link the receptor. These results suggest that mast cells may be an important cell type involved in SEB toxicosis and that release of serotonin may be enhanced by activation of the kinin-kallikrein system.

Acetylcholine↗

Progesterone increases basal 3',5'-cyclic adenosine monophosphate formation and down-regulates the agonist-induced inositol phosphates generation in human term placenta.

Whether the placenta is a target tissue for estrogens and progesterone, and their putative mechanism of action, is still a controversial question in the literature. The effect of progesterone and estradiol on 3',5'-cyclic adenosine monophosphate (cAMP) and inositol phosphates generation in human term placenta was investigated. Placental explants were incubated in vitro for up to 48 h in the absence and in the presence of estradiol, progesterone or both steroids (0.1 mumol/l final concentration in all cases), and were stimulated with terbutaline, a beta-adrenergic agonist, (0.1 mmol/l) or angiotensin II (1 mumol/l). The cAMP content was measured by a competitive protein binding assay, and the generation of labelled inositol phosphates formation in explants prelabelled with 3H-myo-inositol was measured by anion exchange chromatography. Progesterone increased significantly basal cAMP concentrations in comparison with control or estradiol-treated tissues (169 +/- 13, 72 +/- 8, and 69 +/- 2 pmol/g wet wt tissue, mean +/- SEM, respectively). However, following terbutaline stimulation cAMP levels (mean +/- SEM) increased to similar values under all conditions (182 +/- 33, 197 +/- 36, and 237 +/- 17 pmol/g wet wt tissue for control, estradiol-, and progesterone-treated tissues, respectively). Angiotensin II stimulated inositol phosphates generation in placental explants by an average of fivefold, but this increase was significantly reduced in the presence of progesterone (5.2 +/- 0.7, 3.7 +/- 0.4, and 2.2 +/- 0.3 fold increase vs non-angiotensin-stimulated tissues, for control, estradiol-, and progesterone-treated placenta, mean- +/- SEM, respectively). These data suggest that progesterone modulates the formation of second messengers in human placenta at term.

Angiotensin II↗

Septic arthritis in patients with acquired immunodeficiency syndrome with human immunodeficiency virus infection.

We have evaluated the presence and characteristics of septic arthritis in intravenous (iv) drug users with human immunodeficiency virus (HIV) infection. Sixteen patients with both HIV infection and septic arthritis were studied and compared with 5 patients with septic arthritis but no HIV infection. Clinical profile, laboratory findings at the time of onset, localization, causative organisms, mean hospitalization time and presence of complications were the same in HIV positive and HIV negative patients. Staphylococcus aureus was the most commonly isolated organism in both groups. We conclude that septic arthritis in HIV infected iv drug users is not uncommon, it is produced by the same organisms and presents similar characteristics to the ones found in iv drug users without HIV infection. Therefore, the presence of HIV infection does not appear to modify the characteristics of septic arthritis.

Acquired Immunodeficiency Syndrome↗

[Ovulation induction by the chronic administration of naltrexone in a patient with secondary hypothalamic amenorrhea].

An ovulatory cycle was induced by oral administration of a specific opiate antagonist: naltrexone, at a dose of 50 mg/day for 26 days in a woman suffering from secondary hypothalamic amenorrhea. The follicular growth was monitored by ultrasound and serial blood measurement of LH, FSH, E2 and progesterone. The hormonal and ultrasound profiles showed an ovulatory cycle with a single dominant follicle. After discontinuation of the treatment, the patient became amenorrheic again. The gonadotropin as well as estradiol plasma levels declined, to that observed before treatment. Naltrexone may be a useful agent for induction of ovulation in women suffering from hypothalamic amenorrhea.

Adolescent↗