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Biomedical subjects

R Ramirez

Publications and source records attributed to R Ramirez.

At least 37 records · Page 2Linked to original sources

Clinical immunogenicity of measles, mumps and rubella vaccine delivered by the Injex jet injector: comparison with standard syringe injection.

BACKGROUND: The measles, mumps and rubella (MMR) vaccine confers trivalent immunity in >90% of subjects immunized. Alternatives to the use of needles for vaccine administration have recently been made available. We report the safety and efficacy of MMR vaccine delivered by a new needle-free jet injector (Injex) compared with needle syringe administration. METHODS: Forty adolescent subjects were injected bilaterally via needle syringe and jet injector with MMR vaccine and reconstitution buffer. Subjects were blinded as to which device contained the vaccine. Subjects were followed longitudinally for 12 weeks postimmunization, and titers to measles, mumps and rubella immunogens were determined by enzyme immunoassays. Injection pain was quantified using the visual analog pain scale. RESULTS: Adverse events were mild and included injection site soreness (jet injector, 2.5% of subjects; needle, 12.5%), injection site bleeding (jet injector, 0%; needle, 7.5%), malaise (jet injector, 0%; needle, 5%) and fever (jet injector, 0%; needle, 2.5%). All subjects displayed measles titers significantly above baseline during the follow-up. Ninety-five percent of subjects displayed titers above baseline for the mumps antigen vs. 97.5% for rubella. No significant differences in immunogenicity were found between groups receiving the vaccine via the jet injector or the needle syringe at any time during the follow-up (P > 0.05). Injection pain scores were not significantly different between injector types (P > 0.05). CONCLUSIONS: We conclude that the measles, mumps and rubella vaccine can be safely and effectively delivered by the Injex jet injector. This device therefore provides an alternative to standard needle injection and a methodology that might reduce the risk of needle stick accidents.

Adolescent↗

Hydrodynamic theory for granular gases

A granular gas subjected to a permanent injection of energy is described by means of hydrodynamic equations derived from a moment expansion method. The method uses as reference function not a Maxwellian distribution f(M) but a distribution f(0)=Phif(M), such that Phi adds a fourth cumulant kappa to the velocity distribution. The formalism is applied to a stationary conductive case showing that the theory fits extraordinarily well the results coming from our Newtonian molecular dynamic simulations once we determine kappa as a function of the inelasticity of the particle-particle collisions. The shape of kappa is independent of the size N of the system.

Journal Article↗

Detection of immunoglobulin M antibodies to P35 antigen of Toxoplasma gondii for serodiagnosis of recently acquired infection in pregnant women.

We examined the efficiency of detection of immunoglobulin M (IgM) antibodies to a 35-kDa antigen (P35) of Toxoplasma gondii for serodiagnosis of acute infection in pregnant women. A double-sandwich enzyme-linked immunosorbent assay (ELISA) with recombinant P35 antigen (P35-IgM-ELISA) was used for this purpose. On the basis of the clinical history and the combination of results from the toxoplasma serological profile (Sabin-Feldman dye test, conventional IgM and IgA ELISAs, and the differential agglutination test), the patients were classified into three groups: group I, status suggestive of recently acquired infection; group II, status suggestive of infection acquired in the distant past; group III, status suggestive of persisting IgM antibodies. Eighteen (90.0%) of 20 serum samples from group I patients were positive by the P35-IgM-ELISA, whereas none of the 33 serum samples from group II patients were positive. Only 4 (25.0%) of 16 serum samples from group III patients were positive by the P35-IgM-ELISA, whereas all these serum samples were positive by the conventional IgM ELISA. These results indicate that demonstration of IgM antibodies against P35 by the P35-IgM-ELISA is more specific for the acute stage of the infection than demonstration of IgM antibodies by the ELISA that uses a whole-lysate antigen preparation. Studies with sera obtained from four pregnant women who seroconverted (IgG and IgM antibodies) during pregnancy revealed that two of them became negative by the P35-IgM-ELISA between 4 and 6 months after seroconversion, whereas the conventional IgM ELISA titers remained highly positive. The P35-IgM-ELISA appears to be useful for differentiating recently acquired infection from those acquired in the distant past in pregnant women.

Acute Disease↗

NK phenotypic markers and IL2 response in NK cells from elderly people.

Immunosenescence is a process that primarily affects the T cell compartment of the immune system, although age-associated immunological alterations have also been demonstrated in the NK cell phenotype and function. A significant expansion in the number of NK cells is found in aging. The NK cytotoxic capacity of total peripheral blood lymphocytes is also well preserved, not only in healthy elderly people but also in centenarians. However, NK cell killing of K562 is impaired when considered in a per-cell basis, and this defect is associated with defective signal transduction after activation more than a diminished conjugate formation or killing capacity. We have studied the phenotype of NK cells in elderly donors fulfilling the Senieur criteria. We have also studied the capacity of these cells to be activated by IL2 when different NK cell functions, other than cytotoxicity, are considered. Our results confirm the increased percentage of NK cells in the elderly due to the expansion of the CD56dim subset that also show an altered pattern of activation markers, whereas no differences were found in the CD56bright subset. The response of NK cells to IL2 was found to be impaired when proliferation, expression of CD69, and Ca2+ mobilization were considered, whereas TNF-alpha production was not significantly affected. These results suggest that human NK cells do not escape the aging process, although senescence have a differential effect on distinct NK cell biological functions, ranging from severe to negligible impairment, depending on the parameters considered.

Adult↗

Influence of genetic admixture on polymorphisms of drug-metabolizing enzymes: analyses of mutations on NAT2 and C gamma P2E1 genes in a mixed Hispanic population.

OBJECTIVES AND STUDY DESIGN: The genetic basis of two polymorphisms of drug- and carcinogen-metabolizing enzymes, NAT2 (arylamine N-acetyltransferase-2) and CYP2E1 (cytochrome P450 2E1), was studied in genomic deoxyribonucleic acid from 137 healthy, unrelated subjects from a mixed Nicaraguan population. RESULTS: Six point mutations were identified at the coding region of the NAT2 gene, including the most common alleles NAT2*4 (41.6%), NAT2*5B (31.4%), and NAT2*6A (16.8%). The percentage of carriers of two defective genes was 49.6%. The Nicaraguan population studied was in Hardy-Weinberg's disequilibrium for the NAT2 genotype (p < 0.01) and the allele frequencies were significantly different from those of other populations, being intermediate between those of pure Central American Indians and Spanish persons. The frequency of CYP2E1 alleles mutated at the RsaI site (c2 allele; 16.5%) was intermediate between that of Spanish white and Asian subjects. About 5% of the subjects were homozygous for the c2 allele. CONCLUSIONS: These findings indicate a high impact of genetic admixture of populations of Asian origin (Central American Indians) and white persons (Spaniards) on the genetic polymorphisms studied here and suggest that among mixed Hispanics a high heterogeneity of genotypes and phenotypes can be expected depending on the degree of genetic admixture of every subgroup. Therefore different subgroups of mixed Hispanic subjects can exhibit different results when treated with drugs that are inactivated through polymorphic enzymes.

Arylamine N-Acetyltransferase↗

Serum levels of intercellular adhesion molecule 1 (ICAM-1) in patients with colorectal cancer: inhibitory effect on cytotoxicity.

A positive correlation between the level of ICAM-1 in serum and the stage of neoplastic processes has been demonstrated. We studied ICAM-1 serum concentration in 27 colorectal cancer patients and investigated the effect of this molecule on cellular aggregation and toxicity. ICAM-1 serum concentration in the group of patients was significantly higher (P < 0.01) than in normal controls and was related to tumour stage. Patient sera inhibited both the formation of cellular aggregates and the percentage of specific lysis, the effect being lost when the serum was depleted of ICAM-1. These results suggest that the release of soluble ICAM-1 may represent a mechanism of tumour escape.

Aged↗

Plasma growth hormone secretion is impaired in obesity-prone rats before onset of diet-induced obesity.

Sprague-Dawley rats, which become obese (obesity prone) when fed a moderately high-fat (MHF; 32.5% of kcal as fat) diet, have decreased growth hormone (GH) concentrations compared with obesity-resistant rats fed the same diet. To determine whether plasma GH concentrations are different in obesity-prone rats compared with obesity-resistant rats before diet-induced obesity occurs, total integrated GH concentrations were determined in male Sprague-Dawley rats before exposure to the MHF diet. After initial blood sampling, rats were fed an MHF diet for 15 wk, over which time the animals were separated into two discrete populations based on body weight gain. Analysis of GH in episodic blood samples showed that the obesity-prone group had a GH secretion deficit before the onset of obesity (115.2 +/- 12.9 ng . ml-1 . 200 min-1) compared with obesity-resistant rats (237.2 +/- 47.1 ng . ml-1 . 200 min-1). The GH concentration difference was due to a decrease in mean GH peak height in rats that later became obese (34.8 ng/ml) compared with rats that remained lean (74.2 ng/ml). The results suggest that GH secretion impairment exists before dietary challenge or onset of obesity and may contribute to the susceptibility to obesity observed in these animals.

Animals↗

Reduction of the Human Placental Vascular Relaxation to Progesterone by Gestational Diabetes

>Background: We have recently described a dose-dependent, endothelium-independent relaxation to progesterone in human placental arteries and veins. This receptor-operated, cAMP-mediated relaxation may be of value in maintaining adequate blood flow in the placental circulation.Objective: To investigate if gestational diabetes alters this relaxation to progesterone.Study design: Isolated human placental vessels from pregnancies complicated by gestational diabetes and well matched controls (uncomplicated term pregnancies), incubated in Krebs-bicarbonate buffer and submaximally precontracted with KCl, were exposed to cumulative doses of progesterone (0.01-30 µmol/liter), nitroglycerin (0.001-1 µmol/liter), arachidonic acid (0.01-10 µmol/liter), forskolin (0.01-10 µmol/liter) and 5-hydroxytryptamine (serotonin, 0.01-10 µmol/liter).Results: The relaxation to progesterone in vessels from patients with gestational diabetes was reduced by 50-100% in both arteries and veins compared with control (for example, relaxation to 10 µmol/liter progesterone was reduced from 52 +/- 7 to 18.8 +/- 5.4% in arteries and from 58 +/- 8 to 19 +/- 5.2% in veins, n = 7-13, P < 0.05), whereas responses to the other vasoactive agents were unchanged.Conclusion: Based on these results, gestational diabetes significantly reduces the relaxation to progesterone in human placental vessels. This alteration of the relaxation to progesterone may lead to an increase in placental vascular resistance and possibly to a reduction of placental blood flow.

Journal Article↗

Vertical transmission of toxoplasma by human immunodeficiency virus-infected women.

OBJECTIVE: Our goal was to determine the frequency of mother-to-child transmission of Toxoplasma gondii from human immunodeficiency virus-infected mothers who are also chronically infected with T. gondii. STUDY DESIGN: One hundred thirty-eight women were entered into a prospective study of human immunodeficiency virus infection in pregnancy. The women were seen at enrollment, during the third, sixth, and eighth months of pregnancy (except those enrolled later in pregnancy or at delivery), at 2 and 6 months post partum, and at 6-month intervals thereafter through 4 years after delivery. Standardized interviews and physical examinations were performed, and blood was drawn at each visit. Toxoplasma serologic testing was performed on the sample drawn earliest in pregnancy; the Sabin-Feldman dye test for immunoglobulin G antibodies and enzyme-linked immunoassays for immunoglobulins M, A, and E were used. Univariate analysis for categoric variables was performed with chi2 and two-tailed Fisher exact tests, and for continuous variables the Student t test was used. Statistical Analysis System procedures were followed. RESULTS: Twenty-eight of 138 (20.2%) women who had positive test results for human immunodeficiency virus had positive findings of the Sabin-Feldman dye test. Serologic status for T. gondii did not correlate with age, immune status, parity, or drug use. One of 27 children born to women who were seropositive for both human immunodeficiency virus and T. gondii (one child's serologic status for T. gondii was unknown) had Sabin-Feldman dye test antibodies beyond age 6 months (3.7%, 95% confidence interval 0.09% to 18.9%). Among the cohort of human immunodeficiency virus-infected mothers the rate of mother-to-child human immunodeficiency virus transmission did not vary with maternal Toxoplasma status. However, with sample sizes of 28 and 110, respectively, for the mothers who were T. gondii seropositive and seronegative, the power to detect a difference in the human immunodeficiency virus transmission rate between these groups would be relatively small. CONCLUSIONS: Transmission of T. gondii from a chronically infected mother can occur in the setting of a human immunodeficiency virus infection, but this is not a common phenomenon. In a small cohort of human immunodeficiency virus-infected women we did not observe its occurrence among those without severe immunocompromise.

Adult↗

Lymphokine-activated killer (LAK) cell generation from peripheral blood stem cells by in vitro incubation with low-dose interleukin-2 plus granulocyte-macrophage colony-stimulating factor.

Previous reports have demonstrated granulocyte-macrophage colony-stimulating factor (GM-CSF)-mediated enhancement of lymphokine activated killer (LAK) cell function. Based on these studies we have developed a model of LAK cell generation from peripheral blood stem cells (PBSC) from cancer patients by in vitro incubation with low-dose interleukin-2 (IL-2) + GM-CSF. PBSC from seven patients were incubated for 48 h at 37 degrees C in serum-free culture medium supplemented with IL-2 at increasing concentrations (10, 100 or 1000 IU/ml) in the presence or absence of 10 IU/ml GM-CSF. LAK activity generated in cultures with 10 IU/ml IL-2 + GM-CSF was significantly higher than that generated by 10 IU/ml IL-2 and did not differ from LAK generation at optimal concentrations of IL-2 (100 and 1000 IU/ml). PBSC from five additional patients were incubated with low-dose IL-2 + GM-CSF after sequential depletion of the CD4+ and CD8+ T cell subsets. LAK activity was significantly reduced by depletion of both CD4+ and CD8+ T cells and almost completely abolished after depletion of both subsets, suggesting that T cells and not NK cells are the main LAK precursors in this model. Six patients have received two courses of LAK cells generated in vitro by low-dose IL-2 + GM-CSF on day +1 and +8 after PBSC transplant in combination with GM-CSF and IL-2 administration in vivo. The mean LAK activity in peripheral blood of these patients dramatically increased immediately after transplant from a mean of 10% to 43.2% on day +2 and remained increased during the period studied. These results are encouraging and suggest that the administration of in vitro generated LAK cells early after transplant may have a role in the control of minimal residual disease.

Adolescent↗

Upregulation of acidic fibroblast growth factor during development of experimental lung fibrosis.

Fibroblast proliferation and extracellular matrix accumulation are crucial in the pathogenesis of lung fibrosis. Fibroblast growth factor (FGF)-1 participates in both processes, but its role in lung fibrogenesis has not been evaluated. We analyzed the expression of FGF-1 and of FGF receptor (FGFR) in a model of lung fibrosis induced in rats with paraquat plus hyperoxia. Experimental and control animals were killed at 48 h and 2, 4, and 8 wk, and the lungs were studied by in situ hybridization, immunohistochemistry, and Northern blot. In normal lungs, scattered macrophages contained FGF-1. In contrast, at all times examined, the injured lungs exhibited FGF-1 transcript and the immunoreactive protein, mainly in alveolar epithelial cells and macrophages. In advanced fibrotic lesions, fibroblasts also appeared stained. Northern blot corroborated the upregulation of FGF-1 mRNA. FGFR was not observed in normal lungs, whereas it was strongly increased in the damaged lungs and was virtually immunolocalized in the same cell types as the corresponding ligand. These findings suggest that FGF-1 and FGFR are actively synthesized during the development of pulmonary fibrosis.

Animals↗

C1-esterase inhibitor prevents early pulmonary dysfunction after lung transplantation in the dog.

The success of lung transplantation to a large extent depends on effective protection of the graft from ischemic injury after reperfusion. Although mechanisms have not been clarified, the pathologic findings of ischemic injury after reperfusion are similar to adult respiratory distress syndrome, a condition in which the blood coagulation contact system is activated. This study evaluates the effect of C1-esterase inhibitor (C1-INH), the main inhibitor of the blood coagulation contact system, on short-term lung function in a dog model of orthotopic lung transplantation. Twelve lung transplantations were performed after 24 h of ischemic time. Dogs were randomly assigned to receive either vehicle (Control) or C1-INH. After the lung transplantation in the control group, Pao2 decreased by 84% and both the AaPO2 and the Qs/Qt% increased (340 and 530%, respectively, p < 0.01); these parameters remained unchanged in the C1-INH group. The hypoxemia observed in control animals was associated with decreased blood coagulation contact factors, complement consumption, increased expression of adhesion glycoproteins in leukocytes, and extensive intraalveolar and interstitial neutrophil infiltration. In contrast, C1-INH administration prevented hypoxemia, the decrease in blood coagulation contact factors, the activation of the complement system, the increase in expression of leukocyte adhesion molecules, and inflammatory cell infiltrate. This study has demonstrated that in a dog model of lung transplantation, the administration of C1-INH prevents early pulmonary dysfunction, and it suggests that activation of blood coagulation contact system and complement are important mechanisms causing ischemic injury after reperfusion.

Animals↗

Common Caucasoid HLA-A1B8DR3 linkage group and immune responsiveness in a hybrid Venezuelan population: preliminary data.

A study performed on Venezuelans reveals a correlation between the common Caucasoid linkage group HLA-A1 B8 (A*0101, B*0801, DR3-) and increased lymphoproliferative activity stimulated by several concentrations of phytohemagglutin and concanavalin A in comparison to the group of persons possessing either the HLA-A1 (A*0101) antigen or the HLA-B8,DR3 (B*0801,DRB1*03012) haplotype. The increased lymphoproliferative activity was simultaneously present with increased CD16 cell counts and decreased CD3 and total mononuclear counts. A further comparison of lymphocyte population and subpopulation counts in peripheral blood and serum Ig G,A,M levels in the HLA-A1+ B8+ versus the HLA-A1-B8-high-responder individuals revealed increased CD16 cell counts and IgM levels in persons with the common Caucasoid haplotype (HLA-A1 B8). The data may suggest that some of the genes responsible for these levels or genes controlling their expression could be localized in or along the length of the common Caucasoid haplotype HLA-A1 B8 between the A and B loci of the MHC.

Adult↗

The coupling of metabolic to secretory events in pancreatic islets. Glucose-induced changes in mitochondrial redox state.

Mitochondrial NAD+, NADH, NADP+ and NADPH were measured in dispersed pancreatic islet cells incubated in the absence or presence of D-glucose and then exposed for 20 s to 0.5 mg/ml digitonin. The latter treatment resulted in the full release of lactate dehydrogenase without any detectable loss of glutamate dehydrogenase. The permeabilized cells were separated from the incubation medium by centrifugation through an oil layer and their content in pyridine nucleotides measured by a radioisotopic procedure coupled to the classical cycling technique. Relative to basal value, D-glucose, in concentrations of 2.8 and 16.7 mM, caused a concentration-related increase in both the NADH/NAD+ and NADPH/NADP+ ratio. These findings provide the first direct evidence for the induction of a more reduced mitochondrial redox state in glucose-stimulated pancreatic islets.

Animals↗

Anti-CD69 antibodies enhance phorbol-dependent glucose metabolism and Ca2+ levels in human thymocytes. Antagonist effect of cyclosporin A.

The human activation antigen CD69 is an early inducible surface glycoprotein acquired by T cells in the thymus at the stage of positive selection and during activation of mature lymphoid cells both in vivo and in vitro. We have studied the regulatory influence of CD69 activation pathway on the glycolytic process and transduction signals of thymocytes. Treatment of human thymocytes with different anti-CD69 monoclonal antibodies (mAbs), in the presence of submitogenic doses of phorbol ester, produced an enhanced release of lactate without significant alterations in Fru 2,6-P2 levels or phosphofructokinase-2 (PFK-2) and pyruvate kinase activities. A small increase in phosphofructokinase-1 (PFK-1) activity was also detected. Furthermore, anti-CD69 mAb increased the glucose detritiation from [2-3H] and [3-3H]glucose, thus indicating an enhanced flux through hexokinase and PFK-1 steps. In addition, de novo synthesis of diacylglycerol and intracellular Ca2+ levels increased after anti-CD69 mAb treatment. The stimulatory effects of anti-CD69 mAb on both glycolysis and Ca2+ levels were inhibited by cyclosporin A. Because CD69 molecules are present in certain subset populations of immature thymocytes, the ability of anti-CD69 mAb to stimulate the glycolysis, the synthesis of diacylglycerol and the intracellular Ca2+ levels suggest that the activation signals delivered through CD69 molecules could play a role in the thymus cells maturation.

Antibodies, Monoclonal↗

Alteration of human placental vascular tone by antiarrhythmic medications in vitro.

INTRODUCTION: Antiarrhythmic medications are commonly used during pregnancy for treatment of maternal or fetal arrhythmias, but little is known about their effect on human placental vascular tone and, consequently, placental blood flow. The objective of this study was to evaluate the tone responses caused by antiarrhythmic medications in human placental vessels from normal term pregnancies in vitro. METHODS AND RESULTS: Isolated human placental arteries and veins from uncomplicated term pregnancies incubated in Krebs'-bicarbonate under 5% oxygen/5% carbon dioxide/balance nitrogen (PO2 35 to 38 torr) were exposed to cumulative doses of quinidine, procainamide, lidocaine, flecainide, propranolol, amiodarone, verapamil, digoxin, and adenosine after submaximal contraction with 5-hydroxytryptamine. The study was conducted both in the presence and absence of endothelium. The addition of the tested medications caused a significant, dose-dependent relaxation of human placental arteries and veins except for adenosine, which induced a sustained, dose-dependent contraction of human placental vessels regardless of the presence or absence of tone. Removal of the endothelium did not alter these responses. CONCLUSIONS: Based on these results, the medications tested should have no decremental effect on placental blood flow, with the possible exception of adenosine, which causes significant, dose-dependent contraction of human placental vessels in vitro. Should similar contraction be present in vivo, it may have an adverse effect on the fetus when administering adenosine to pregnant women at term or during labor.

Anti-Arrhythmia Agents↗