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Biomedical subjects

A Jaramillo

Publications and source records attributed to A Jaramillo.

At least 37 records · Page 2Linked to original sources
PubMed1997

Neonatal activation of CD28 signaling overcomes T cell anergy and prevents autoimmune diabetes by an IL-4-dependent mechanism.

Optimal T cell responsiveness requires signaling through the T cell receptor (TCR) and CD28 costimulatory receptors. Previously, we showed that T cells from autoimmune nonobese diabetic (NOD) mice display proliferative hyporesponsiveness to TCR stimulation, which may be causal to the development of insulin-dependent diabetes mellitus (IDDM). Here, we demonstrate that anti-CD28 mAb stimulation restores complete NOD T cell proliferative responsiveness by augmentation of IL-4 production. Whereas neonatal treatment of NOD mice with anti-CD28 beginning at 2 wk of age inhibits destructive insulitis and protects against IDDM by enhancement of IL-4 production by islet-infiltrating T cells, administration of anti-CD28 beginning at 5-6 wk of age does not prevent IDDM. Simultaneous anti-IL-4 treatment abrogates the preventative effect of anti-CD28 treatment. Thus, neonatal CD28 costimulation during 2-4 wk of age is required to prevent IDDM, and is mediated by the generation of a Th2 cell-enriched nondestructive environment in the pancreatic islets of treated NOD mice. Our data support the hypothesis that a CD28 signal is requisite for activation of IL-4-producing cells and protection from IDDM.

Animals↗
PubMed1997

Effects of heparin-coating of cardiopulmonary bypass circuits on leukocytes during simulated extracorporeal circulation.

Heparin-coated circuits used during extracorporeal circulation reduce many postoperative complications occurring after heart surgery. Such complications are partly related to leukocyte activation with subsequent release of active substances, e.g. oxygen free radicals, myeloperoxidase and lactoferrin. This experiment was performed to elucidate a possible influence of heparin-coating on leukocytes. A 2-h-long simulated extracorporeal circulation was performed on two groups of five extracorporeal circulation circuits, primed with heparinized, fresh whole human blood and Ringer's solution. Heparin-coated circuits (HC group) were compared with uncoated circuits (NC group). Oxygen free radical production was estimated by determination of malonyldialdehyde in plasma and erythrocyte suspension. Granulocyte activation was measured in terms of myeloperoxidase and lactoferrin release. Time-related changes in leukocyte subset counts were analysed. Heparin-coating diminished myeloperoxidase and lactoferrin release. There were significant inter-group differences after 90 and 120 min of extracorporeal circulation for myeloperoxidase (101 (12) microg/l and 107(12) microg/l in the HC group versus 154(20) microg/l and 174(23) microg/l in the NC group), and after 120 min of extracorporeal circulation for lactoferrin (78(5) microg/l in the HC group versus 212(49) microg/l in the NC group). No significant changes of MDA concentration were observed in plasma or erythrocytes; however, a tendency towards lower MDA levels was seen after 90 and 120 min of extracorporeal circulation in the NC group. Neutrophil, monocyte and eosinophil numbers decreased significantly in the NC group but were unchanged in the HC group, as were lymphocyte counts. Heparin-coated extracorporeal circulation circuits significantly reduce granulocyte activation and better preserve the number of circulating neutrophils, eosinophils and monocytes, but do not change oxygen free radical production during simulated extracorporeal circulation.

Anticoagulants↗
PubMed1995

Genetic linkage of thymic T-cell proliferative unresponsiveness to mouse chromosome 11 in NOD mice. A possible role for chemokine genes.

Thymic and peripheral T-cells from NOD mice display a proliferative unresponsiveness on stimulation through the T-cell receptor/CD3 complex. Interleukin 4 reverses NOD T-cell unresponsiveness in vitro and prevents the onset of diabetes in vivo, suggesting a causal relationship between the T-cell unresponsiveness and diabetes susceptibility in NOD mice. Both quantitative trait loci analysis of BXD recombinant inbred mice and linkage analysis of NOD outcross populations reveal that the control of NOD thymic T-cell proliferative unresponsiveness genetically maps to a central region on mouse chromosome 11, which includes the beta-chemokine gene family. This finding raises the possibility that a beta-chemokine(s) may regulate T-cell unresponsiveness as well as diabetes susceptibility in NOD mice.

Animals↗
PubMed1994

Insulin dependent diabetes mellitus in the non-obese diabetic mouse: a disease mediated by T cell anergy?

The non-obese diabetic (NOD) mouse spontaneously develops autoimmune type I insulin-dependent diabetes mellitus (IDDM) with a similar immunopathological profile to the human disease. Development of the disease in both the NOD mouse and in humans is under polygenic control and influenced by many environmental factors. Diabetes results from a specific T cell-mediated destruction of pancreatic insulin-producing islet beta cells. Both CD4 and CD8 T cells as well as macrophages are required for the development of diabetes in NOD mice. An intriguing similarity between murine and human diabetes is a T cell proliferative unresponsiveness (anergy) that may be a susceptibility factor to disease onset. Defective communication between antigen-presenting cells (APC) and T cells, and/or an aberrant production or activity of inflammatory cytokines (e.g. chemokines) in the thymus and periphery (e.g. pancreas) may account for the unresponsiveness of regulatory T cells leading to a loss of immunological tolerance to beta cell autoantigens in NOD mice and in diabetic humans.

Animals↗
PubMed1993

Surfactant-modified graphite surfaces in biological analysis: ionic strength and ion charge effects.

Previous work with rough pyrolytic graphite and glassy carbon electrodes demonstrated that surfactant assembly at these two structurally and chemically different surfaces was similar, with surfactants adsorbing head on. Improvement in response of biological molecules was attributed to the formation of a dynamic, renewable surface. Furthermore, surfactants provided a favorable hydrophobic-hydrophilic environment for the response of selected catechols. Surfactants could also be used to control selectivity if needed. In this work ionic strength and cation charge effects on response of catechols in surfactant solutions are investigated. The results illustrate the relative importance of electrostatic and hydrophobic interactions at graphite to the response of probes with combined hydrophobic and hydrophilic properties. Furthermore, the results show that although catechol-surface interactions are significantly affected by ionic strength and electrolyte charge, surfactant-surface and surfactant-probe interactions are not significantly affected, indicating that surfactants serve as an effective ionic buffer. The results presented here indicate that surfactant assembly at the surface is best at low ionic strength. These results also verify the importance of a favorable hydrophobic and hydrophilic environment to catechol response which can be provided by the surfactants when needed.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Interleukin 4 reverses T cell proliferative unresponsiveness and prevents the onset of diabetes in nonobese diabetic mice.

Beginning at the time of insulitis (7 wk of age), CD4+ and CD8+ mature thymocytes from nonobese diabetic (NOD) mice exhibit a proliferative unresponsiveness in vitro after T cell receptor (TCR) crosslinking. This unresponsiveness does not result from either insulitis or thymic involution and is long lasting, i.e., persists until diabetes onset (24 wk of age). We previously proposed that it represents a form of thymic T cell anergy that predisposes to diabetes onset. This hypothesis was tested in the present study by further investigating the mechanism responsible for NOD thymic T cell proliferative unresponsiveness and determining whether reversal of this unresponsiveness protects NOD mice from diabetes. Interleukin 4 (IL-4) secretion by thymocytes from > 7-wk-old NOD mice was virtually undetectable after treatment with either anti-TCR alpha/beta, anti-CD3, or Concanavalin A (Con A) compared with those by thymocytes from age- and sex-matched control BALB/c mice stimulated under identical conditions. NOD thymocytes stimulated by anti-TCR alpha/beta or anti-CD3 secreted less IL-2 than did similarly activated BALB/c thymocytes. However, since equivalent levels of IL-3 were secreted by Con A-activated NOD and BALB/c thymocytes, the unresponsiveness of NOD thymic T cells does not appear to be dependent on reduced IL-2 secretion. The surface density and dissociation constant of the high affinity IL-2 receptor of Con A-activated thymocytes from both strains are also similar. The patterns of unresponsiveness and lymphokine secretion seen in anti-TCR/CD3-activated NOD thymic T cells were also observed in activated NOD peripheral spleen T cells. Exogenous recombinant (r)IL-2 only partially reverses NOD thymocyte proliferative unresponsiveness to anti-CD3, and this is mediated by the inability of IL-2 to stimulate a complete IL-4 secretion response. In contrast, exogenous IL-4 reverses the unresponsiveness of both NOD thymic and peripheral T cells completely, and this is associated with the complete restoration of an IL-2 secretion response. Furthermore, the in vivo administration of rIL-4 to prediabetic NOD mice protects them from diabetes. Thus, the ability of rIL-4 to reverse completely the NOD thymic and peripheral T cell proliferative defect in vitro and protect against diabetes in vivo provides further support for a causal relationship between this T cell proliferative unresponsiveness and susceptibility to diabetes in NOD mice.

Animals↗
PubMed1993

Thymic T cell anergy in autoimmune nonobese diabetic mice is mediated by deficient T cell receptor regulation of the pathway of p21ras activation.

Thymic T cell anergy, as manifested by thymocyte proliferative unresponsiveness to antigens expressed in the thymic environment, is commonly believed to mediate the acquisition of immunological self-tolerance. However, we previously found that thymic T cell anergy may lead to the breakdown of tolerance and predispose to autoimmunity in nonobese diabetic (NOD) mice. Here, we show that NOD thymic T cell anergy, as revealed by proliferative unresponsiveness in vitro after stimulation through the T cell receptor (TCR), is associated with defective TCR-mediated signal transduction along the PKC/p21ras/p42mapk pathway of T cell activation. PKC activity is reduced in NOD thymocytes. Activation of p21ras is deficient in quiescent and stimulated NOD T cells, and this is correlated with a significant reduction in the tyrosine phosphorylation of p42mapk, a serine/threonine kinase active downstream of p21ras. Treatment of NOD T cells with a phorbol ester not only enhances their p21ras activity and p42mapk tyrosine phosphorylation but also restores their proliferative responsiveness. Since p42mapk activity is required for progression through to S phase of the cell cycle, our data suggest that reduced tyrosine phosphorylation of p42mapk in stimulated NOD T cells may abrogate its activity and elicit the proliferative unresponsiveness of these cells.

Animals↗
PubMed1993

Effect of nickel sulfide on induction of interleukin-1 and phagocytic activity.

Rat peritoneal macrophages were treated with crystalline nickel sulfide (NiS), washed, and then tested for interleukin-1 (IL-1) production and phagocytosis of IgG-opsonized sheep red blood cells (SRBC). Pretreatment of peritoneal macrophages with crystalline NiS did not affect their ability to produce IL-1. In contrast, pretreatment of peritoneal macrophages with crystalline NiS inhibited the phagocytic activity of the peritoneal macrophage. This inhibitory activity was due to an effect on the internalization step of the phagocytic process. The binding step of this process was not affected by exposure to crystalline NiS. The overall number of Ig-SRBC that interacted with each macrophage was not different in treated or untreated cultures. This interaction is mediated through Fc receptors on the macrophage membrane. This result suggests that crystalline NiS does not modulate the expression of Fc receptors by peritoneal macrophages. The results described in this study suggest that crystalline NiS has a potent immunomodulatory effect on macrophage phagocytic activity.

Animals↗
PubMed1992

Characteristics of the inhibition of interferon-alpha/beta production after crystalline nickel sulfide exposure.

Murine L-929 cells were treated with crystalline nickel sulfide (NiS), washed, and then exposed to polyriboinosinic-polyribocytidylic acid (Poly I:C) to induce interferon-alpha/beta (IFN-alpha/beta). Addition of crystalline NiS at different time points, from 24 hr prior to IFN induction (pretreatment) up to 12 hr after IFN induction, resulted in significant inhibition of IFN-alpha/beta production. In addition, 24-hr pretreatment of L-929 cells with crystalline NiS resulted in significantly decreased production of IFN-alpha/beta even 120 hr after addition of IFN inducer. IFN-alpha/beta at a known concentration was titered by means of a viral plaque reduction assay in crystalline NiS-treated L-929 cell cultures. Crystalline NiS did not show a significant inhibitory effect on the antiviral activity of IFN on L-929 cells as compared to controls. The results described here suggest that NiS has a rapid and a long-lasting inhibitory activity on the production of IFN-alpha/beta.

Animals↗
PubMed1992

Potentiation of lymphocyte proliferative responses by nickel sulfide.

Crystalline nickel sulfide (NiS) induced a spleen cell proliferation that resembles a mixed lymphocyte reaction (MLR). It depended on cell-cell interaction, induced high levels of interleukin-1 (IL-1) and interleukin-2 (IL-2) and the responding cell subpopulation was composed of CD4+ T lymphocytes. Furthermore, the proliferation was inhibited in a dose-dependent manner by magnesium. Crystalline NiS also increased significantly the spleen cell proliferative response to concanavalin A (Con A) and lipopolysaccharide (LPS) with magnesium potentiating the combined effects of crystalline NiS and mitogens. Interestingly, crystalline NiS did not show any effect on the induction of IL-2 by Con A. The results described herein suggest that crystalline NiS can potentiate both antigenic (MLR) and mitogenic (Con A and LPS) proliferative responses in vitro. Crystalline NiS appears to potentiate these responses by acting in the form of ionic nickel on several intracellular targets for which magnesium ions have different noncompetitive interactions. The effects of magnesium on the potentiating action of crystalline NiS are different depending upon the type of primary stimulatory signal for proliferation (mitogenic or antigenic).

Adjuvants, Immunologic↗
PubMed1992

Modulation of immune responses by cyclo-oxygenase inhibitors during intraocular inflammation.

The effects of cyclooxygenase inhibitors flurbiprofen and indomethacin on the inflammatory response and immune reactions induced by S-antigen in the rat eye were studied. The treatment with flurbiprofen and indomethacin administered subcutaneously every 12 hours, commenced on the day of S-antigen injection and was continued until the termination of the experiment (12 days). Flurbiprofen reduced vasodilation and the inflammatory exudate into the anterior chamber by 38% and 36% respectively while inhibiting polymorphonuclear leukocytes infiltration by 57% without affecting monocytes infiltration. Indomethacin had similar but greater effects than flurbiprofen on all these parameters. However, the differences between the mean values of the two compounds were not significant. Both compounds also attenuated spleen cell proliferation, serum IgG levels to S-antigen and interferon-gamma levels in the aqueous humor. The level of prostaglandin E2, but not of leukotriene B4, was increased in the untreated inflamed uveal tissues and this increase was significantly inhibited by flurbiprofen and indomethacin. The results of this study suggest that cyclooxygenase products are involved in the normal development of both humoral and cellular immune response in the experimental uveitis.

Animals↗
PubMed1992

Flowmetric evaluation of internal mammary artery flap during repair of aortic coarctation.

Resection of the internal shelf through a longitudinal aortotomy and widening with the free end of the left in situ internal mammary artery (IMA) were steps in correction of aortic coarctation with isthmus hypoplasia in nine patients aged 9-14 (mean 10.5) years. Electromagnetic flowmetry was performed on the left IMA before and after the repair. The essential finding was considerably increased mean blood flow in the IMA flap during cross-clamping proximal to the completed repair, from 53 +/- 48 to 430 +/- 74 ml/min (378 +/- 78%). The IMA thus is a powerful conduit with extraordinary flow capacity when runoff is appropriate. Integration of IMA as a viable flap in the repair of aortic coarctation implies that this artery increases its collateral flow contribution to the distal aorta.

Adolescent↗
PubMed1992

A "new" intraabdominal artery. The pedicled right gastroepiploic artery for myocardial revascularization.

The right gastroepiploic artery (GEA) was used as a pedicled conduit for direct coronary artery revascularization in 20 patients presenting with more or less exhausted saphenous vein resources. The early angiographic patency of the GEA conduit appears to be satisfactory when it is connected to the right coronary artery system. A distinct disadvantage of GEA grafting is the necessity to enter the abdominal cavity, which may lead to probably rare and as yet unrecognized morbidity. Future abdominal surgery may injure the GEA conduit unless its topographic relations to the prepyloric antrum, liver and diaphragm are properly recognized. The surgeon must then be prepared to encounter antegastric, retrogastric, antehepatic, transhepatic and retrohepatic routes of the redirected intraabdominal artery. The present paper addresses this problem. Preoperative angiography of the celiac trunk and superior mesenteric artery may be helpful in decision-making when a patient reports or records show that a graft has been harvested from the abdominal cavity.

Arteries↗
PubMed1989

Effects of amorphous and crystalline nickel sulfide on induction of interferons-alpha/beta and -gamma and interleukin-2.

Pretreatment of rat spleen cells with crystalline or amorphous nickel sulfide (NiS) did not inhibit induction of interferon-gamma or interleukin-2 by concanavalin A. In contrast, pretreatment of murine L-929 cells with crystalline NiS inhibited severely IFN-alpha/beta induction by polyriboinosinic-polyribocytidylic acid, while amorphous NiS did not show any effect. This difference in the effects of both forms of NiS on the spleen and L-929 cells correlated with the cellular internalization of the compound; L-929 cells actively phagocytosed crystalline NiS while the uptake of amorphous NiS by the same type of cells was minimal. The uptake of both crystalline and amorphous NiS by spleen cells was very low.

Animals↗
PubMed1989

[Tuberculin response in school children in Pacasmayo, Peru].

To shed some light on the controversy over the protective effect of BCG vaccine and the usefulness of the tuberculin test in countries with a high prevalence of tuberculosis, in September and October 1987 the test was administered to 440 primary school students in the province of Pacasmayo, Peru. The subjects, both vaccinated with BCG and unvaccinated, ranging from 6 to 10 years of age and coming from rural and urban areas with corresponding vaccination coverage of 55 and 60%, were selected by cluster sampling. The tuberculin reaction was negative in 71% of the vaccinated children and 83% of the unvaccinated children, positive in 16 and 11%, respectively, and inconclusive in the remaining subjects. The results suggest that BCG only prevents progression to the serious forms of the infection. The positive reaction indicates infection or reinfection with Mycobacterium tuberculosis regardless of vaccination status. A negative response in unvaccinated children almost always indicates the absence of infection. The inconclusive results in the unvaccinated children could be the result of a nonspecific allergy and, in the vaccinated children, of persistence of the change produced by M. tuberculosis. The percentage of infected schoolchildren was similar to that in other areas of the country with similar epidemiological characteristics. The tuberculin test appears to be especially important when more than five years have passed since vaccination.

BCG Vaccine↗