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M Rincon

Publications and source records attributed to M Rincon.

17 recordsLinked to original sources
PubMed2001

Carbonic anhydrase II is an AP-1 target gene in osteoclasts.

c-Fos, a member of the AP-1 family of transcription factors, is necessary for osteoclast differentiation but to date, none of the osteoclast-phenotypic markers have been identified as AP-1 target genes. Here, we demonstrate that carbonic anhydrase II (CA II), an enzyme necessary for osteoclast activity, is transcriptionally upregulated by c-Fos/AP-1. A functional AP-1 binding site is present in the CA II promoter and is necessary for this regulation. Furthermore, we show that AP-1 binding activity, mainly composed of Fra-2 and JunD, is induced by treatment of bone marrow cultures with the osteoclastogenic hormone 1,25 dihydroxyvitamin D(3). Fra-2 and JunD are found in mature osteoclasts as well. Thus, our data demonstrate that cFos/AP-1 can directly regulate the expression of this osteoclast marker and that AP-1 activity is upregulated in osteoclast progenitors in response to osteoclastogenic signals.

Animals↗
PubMed2001

Pneumocystis carinii pneumonia in heart transplant recipients.

OBJECTIVES: In spite of the high prevalence of Pneumocystis carinii (PC) pneumonia in immunocompromised patients, little is known about the epidemiological characteristics of this infection, and whether the cases of PC pneumonia in immunosuppressed patients are the result of a reactivation of a latent infection or a due to a recent infection is unknown. The aim of this study was to provide information about the epidemiological characteristics of PC pneumonia in a cohort of heart transplant (HT) recipients when compared with the epidemiology of PC infection in a cohort of chronic sputum producers (CSP) representative of the general population of the same geographical area. METHODS: We identified all the cases of PC pneumonia in the cohort of 72 subjects who underwent cardiac transplantation at our institution between January 1991 and December 1996 and compared them with the cases of PC infection identified in a non-selected cohort of 34 CSP. This second group was included to obtain an approximation of the frequency of PC carriers in the general population. Identification of PC was accomplished through customary stain techniques and immunofluorescence with monoclonal antibodies. RESULTS: Of the 72 HT recipients four (5.5%) developed PC pneumonia, but one had two episodes. Only one had received primary chemoprophylaxis, but developed PC pneumonia 2 months after discontinuing prophylactic therapy. PC pneumonia episodes were produced 53, 102, 230, 181 and 772 days after the moment of transplant, respectively. PC was identified in two (5.8%) of the 34 CSP. No significant differences were found when the accumulative incidences of PC pneumonia in HT patients and PC infection in CSP were compared (P=0.7). CONCLUSIONS: The frequency of PC pneumonia among HT patients is the same as the frequency of PC infection in the general population. This observation and the long interval between transplantation and the development of PC pneumonia observed in the study support the hypothesis that the occurrence of PC pneumonia in immunocompromised patients might be from a new infection rather than from the reactivation of latent organisms. Therefore, continuous prophylaxis might be indicated in areas with a high prevalence of PC for patients at highest risk.

Aged↗
PubMed2001

Self-efficacy, depressive symptoms, and patients' expectations predict outcomes in asthma.

BACKGROUND: Certain psychosocial variables are relatively unexplored as possible predictors of asthma outcomes. OBJECTIVE: To determine if asthma self-efficacy, depressive symptoms, and unrealistic expectations predict urgent care use and change in health-related quality of life measured by the Asthma Quality of Life Questionnaire and the SF-36 during 2 years. RESEARCH DESIGN: Prospective cohort study in a primary care internal medicine practice at a tertiary care center in New York City. PATIENTS: Adults with moderate asthma who were fluent in either English or Spanish. MEASUREMENTS: At enrollment patients were interviewed in-person and completed a series of questionnaires including the Asthma Quality of Life Questionnaire (AQLQ), the SF-36, the Asthma Self-efficacy Scale, the Geriatric Depression Scale, and open-ended questions regarding their expectations of treatment. Patients also completed the AQLQ and SF-36 at various time intervals throughout the study and were interviewed by telephone every 3 months to record recent hospitalizations, emergency department visits and nonroutine office visits for asthma. RESULTS: A total of 224 patients were followed for a mean of 23.8 months. In hierarchical analysis, independent predictors of lower AQLQ scores were less self-efficacy, more depressive symptoms, expecting to be cured of asthma, requiring methylxanthines, being Hispanic or black, and having difficult or very difficult access to asthma care (all at P <0.05). Similar predictors were found for lower SF-36 scores. Another outcome, use of urgent care, was required by 60% of patients during the study period. Predictors of using urgent care were having more depressive symptoms, expecting a cure, being female, requiring oral beta-agonists, and having a history of prior hospitalizations for asthma (all at P <0.05). CONCLUSIONS: Less asthma self-efficacy, more depressive symptoms, and unrealistic expectations predict worse asthma outcomes. These relatively unexplored patient-centered variables in asthma are potentially modifiable and may offer new ways to intervene to improve asthma outcomes.

Adolescent↗
PubMed2000

Defective Th function induced by a dominant-negative cAMP response element binding protein mutation is reversed by Bcl-2.

cAMP response element binding protein (CREB) is a critical regulator of diverse stimulus-dependent transcriptional events. Following TCR stimulation, CREB is rapidly induced in CD4+ Th cell precursors, but not in effector Th cells. However, its role in mature T cell function is incompletely defined. Transgenic mice expressing a CREB dominant-negative (dn) mutation in the T cell lineage exhibited normal T cell development in the thymus, normal T cell homeostasis in the periphery, and normal T cell clonal expansion following Ag challenge. However, this mutation caused selective inhibition of Th cell function in vitro and in vivo, and increased susceptibility of Th cells to activation-induced cell death. Th cells expressing the CREB-dn mutation contained reduced levels of the inhibitor of programmed cell death, BCL-2; overexpression of BCL-2 in transgenic mice reversed both susceptibility to activation-induced cell death in CREB-dn T cells and the defect in effector cytokine production. Thus, CREB plays a critical role in Th cell function and development of Th cell-mediated adaptive immune responses, at least in part, by inhibiting stimulus-dependent cell death.

Alanine↗
PubMed2000

Involvement of nuclear factor of activated T cells activation in UV response. Evidence from cell culture and transgenic mice.

Mammalian cells respond to UV radiation by signaling cascades leading to activation of transcription factors, such as activated protein 1, NFkappaB, and p53, a process known as the "UV response." Nuclear factor of activated T cells (NFAT) was first identified as an inducible nuclear factor in immune response and subsequently found to be expressed in other tissues and cells. To date, however, the regulation and function of NFAT in tissues and cells, other than the immune system, are not well understood. In this study, we demonstrate that UV radiation activates NFAT-dependent transcription through a calcium-dependent mechanism in mouse epidermal JB6 cell lines, as well as in the skin of NFAT-luciferase reporter transgenic mice. Exposure of JB6 cells to UV radiation leads to the transactivation of NFAT in a dose-dependent manner. A23187 had a synergistic effect with UV for NFAT induction, whereas pretreatment of cells with nifedipine, a calcium channel blocker, dramatically impaired the NFAT activity induced by either UV or UV plus A23187. Calcium-dependent activation of NFAT by UV was further confirmed by an in vivo study using NFAT-luciferase reporter transgenic mice. These results demonstrated that UV radiation is a strong activator for skin NFAT transactivation through calcium-dependent pathways, suggesting that NFAT activation may be a part of the UV response.

Animals↗
PubMed2000

NF-kappa B activation by the pre-T cell receptor serves as a selective survival signal in T lymphocyte development.

Activation of the transcription factor NF-kappa B and pre-T cell receptor (pre-TCR) expression is tightly correlated during thymocyte development. Inhibition of NF-kappa B in isolated thymocytes in vitro results in spontaneous apoptosis of cells expressing the pre-TCR, whereas inhibition of NF-kappa B in transgenic mice through expression of a mutated, superrepressor form of I kappa B alpha leads to a loss of beta-selected thymocytes. In contrast, the forced activation of NF-kappa B through expression of a dominant-active I kappa B kinase allows differentiation to proceed to the CD4(+)CD8(+) stage in a Rag1(-/-) mouse that cannot assemble the pre-TCR. Therefore, signals emanating from the pre-TCR are mediated at least in part by NF-kappa B, which provides a selective survival signal for developing thymocytes with productive beta chain rearrangements.

Animals↗
PubMed1999

Molecular basis of T-cell differentiation.

In summary, a multitude of regulatory systems are employed to cause the selective activation of target cytokine genes in Th1 and Th2 effector cells. These mechanisms involve both positive and negative regulation and employ at least three kinds of mechanisms. In the first, selective expression of transcription factors such as GATA3 in Th2 cells and the homeobox gene HLX in Th1 cells occurs, and appears in both cases to play a causal role. Another example of this would be c-maf, discovered by the Glimcher laboratory. A second mechanism is by the selective accumulation of protein through posttranscriptional mechanisms. Thus, junB accumulates in Th2 cells despite the fact that the junB mRNA levels are not different between Th1 and Th2 cells. Finally, the selective use of signaling pathways, in the case studied here MAP kinase pathways, leads to the selective activation of target genes. We believe that transcriptional up-regulation of rac2 leads to the coupling of both the p38 and JNK MAP kinase pathways to the T-cell receptor and/or costimulatory receptors, thereby providing a lineage-specific signal.

Cell Differentiation↗
PubMed1998

Consequences of intrathymic TCR engagement by partial agonist on selection events and peripheral T cell activation program.

Functions elicited from mature T cells depend on the nature of the Ag. Thus, an agonist induces a larger set of cytokine responses than a partial agonist. Additionally, Ags present in the thymus influence both the selection of TCRs generated by gene rearrangement and the potential functional program of developing thymocytes. This can be approached by analysing the development of T cells in mice expressing the same transgenic TCR (tgTCR) under different conditions of intrathymic selection. H-2Kbm8 was found to act as a partial agonist for CD8+ T cells expressing a tgTCR specific for the H-2Kb alloantigen. Intrathymic exposure to full or to partial agonist affected the development of thymocytes at different stages, consistent with the respective CD8-independent and -dependent characteristic of the tgTCR/Ag interaction. The presence of the partial agonist led to the accumulation of a major population of thymocytes (tgTCR(high) CD4- CD8(low)) originating from TCR engagement at the immature single-positive CD8(low) stage as evidenced by: 1) results from reaggregated thymic organ culture in the presence of H-2(k/bm8) thymic stromal cells; 2) the absence of CD4+ thymocytes, the development of which depends on rearrangements of endogenous TCR alpha genes; and 3) the identification of the CD8(low) thymocytes as cycling cells. Peripheral CD8(low) T cells selected in an H-2(k/bm8) thymus expressed a partial functional program in response to H-2Kb, akin to the response of CD8(high) T cells to a partial agonist. The analysis of the molecular bases for partial reactivity revealed a correlation with inefficient AP-1, but efficient NF-kappaB transactivation.

Animals↗
PubMed1998

A new method to isolate large numbers of rabbit osteoclasts and osteoclast-like cells: application to the characterization of serum response element binding proteins during osteoclast differentiation.

We have developed a new method that allows the purification of large numbers of both authentic osteoclasts (OCs) and in vitro differentiated osteoclast-like cells (OCLs) from rabbits. We characterized the OCLs in terms of the expression of different phenotypic markers of OC differentiation and their ability to resorb bone. The method provides a system for performing biochemical and molecular studies of OC differentiation and function in a single species. We used this system to characterize the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on the expression of proteins that bind to the serum response element (SRE) of the c-fos promoter. We found that OCLs and OCs displayed similar SRE-binding activities, including the serum response factor (SRF). This pattern is established in a time-dependent and cell-specific manner in response to long-term treatment of rabbit bone marrow by 1,25(OH)2D3. Thus, 1,25(OH)2D3 can modulate SRF and/or SRF-related protein. This finding may contribute to understanding the role of c-Fos in the regulation of OC differentiation.

Animals↗
PubMed1997

Blocking activator protein-1 activity, but not activating retinoic acid response element, is required for the antitumor promotion effect of retinoic acid.

Retinoic acid is one of the most promising drugs for chemotherapy and chemoprevention of cancer. Either blocking activator protein-1 (AP-1) activity or activating retinoic acid response element (RARE) have been proposed to be responsible for its antitumor activity. However, evidence for this hypothesis is lacking in vivo studies. To address this issue, we used an AP-1-luciferase transgenic mouse as a carcinogenesis model and new synthetic retinoids that are either selective inhibitors of AP-1 activation or selective activators of the RARE. The results showed that the SR11302, an AP-1 inhibition-specific retinoid, and other AP-1 inhibitors such as trans-retinoic acid and fluocinolone acetonide, markedly inhibit both 12-O-tetradecanoylphorbol-13-acetate-induced papilloma formation and AP-1 activation in 7,12-dimethyl benz(a)anthracene-initiated mouse skin (P < 0.05). In contrast, repeated applications of SR11235, a retinoid with RARE transactivating activity, but devoid of AP-1 inhibiting effect, did not cause significant inhibition of papilloma formation and AP-1 activation (P > 0.05). These results provide the first in vivo evidence that the antitumor effect of retinoids is mediated by blocking AP-1 activity, but not by activation of RARE.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1996

Effect of anti-interleukin 12 treatment on murine lyme borreliosis.

The effect of anti-interleukin (IL-12 treatment on Lyme borreliosis in C3H/HeN (C3H) mice was assessed because other studies have implicated CD4+ T cell helper (Th) type 1 responses in the genesis of disease caused by Borrelia burgdorferi. Infection of inbred mice with B. burgdorferi results in varying degrees of arthritis: BALB/c mice develop mild disease and C3H mice develop severe arthritis that is most pronounced 2-4 wk after infection. Since IL-12 is a major inducer of Th1 responses, we blocked this cytokine in vivo in B. burgdorferi infected C3H mice, and evaluated the effects of treatment on the development of arthritis at the peak of acute joint inflammation (14 d) and in the resolution phase (60 d) of disease. As expected, intraperitoneal administration of an anti-IL-12 monoclonal antibody (mAb) to C3H mice resulted in a decrease in both IFN-gamma and B. burgdorferi-specific IgG2a in serum, indicative of diminished Th1 responses. No IL-4 production was detected in serum of anti-IL-12 mAb treated or control mice. IgG1 and IgG2b levels did not increase in B. burgdorferi infected mice treated with anti-IL-12 mAb compared with controls suggesting that Th2 responses were not affected. Nevertheless, CD4+ T cells from both control and anti-IL-12 mAb treated mice had similar in vitro responses to B. burgdorferi antigens. Treatment with anti-IL-12 mAb produced a significant reduction in peak arthritis severity, and an increase in the number of spirochetes in ear tissue. These data show that treatment of B. burgdorferi infected mice with anti-IL-12 mAb results in a reduction of the Th1 and/or innate immune responses in vivo and a reduction in the severity of acute murine Lyme arthritis.

Animals↗
PubMed1996

Regulation of AP-1 and NFAT transcription factors during thymic selection of T cells.

The ability of thymocytes to express cytokine genes changes during the different stages of thymic development. Although CD4- CD8- thymocytes are able to produce a wide spectrum of cytokines in response to a T-cell receptor (TcR)-independent stimulus, as they approach the double-positive (DP) CD4+ CD8+ stage, they lose the ability to produce cytokine. After the DP stage, thymocytes become single-positive CD4+ or CD8+ thymocytes which reacquire the ability to secrete cytokines. In an attempt to understand the molecular basis of this specific regulatin, we use AP-1-luciferase and newly generated NFAT-luciferase transgenic mice to analyze the transcriptional and DNA-binding activities of these two transcription factors that are involved in the regulation of cytokine gene expression. Here, we show that both AP-1 and NFAT transcriptional activities are not inducible in the majority of DP cells but that during the differentiation of DP cells to the mature single-positive stage, thymocytes regain this inducibility. Subpopulation analysis demonstrates that this inducibility is reacquired at the DP stage before the down-modulation of one of the coreceptors. Indeed AP-1 inducibility, just like the ability to express the interleukin-2 gene, is reacquired during the differentiation of DP TcRlow CD69low heat-stable antigen (HSA)high thymocytes to DP TcRhigh CD69high HSAhigh cells, which is considered to be the consequence of the first signal that initiates positive selection. We therefore propose that the inability of DP thymocytes to induce AP-1 and NFAT activities is one of the causes for the lack of cytokine gene expression at this stage and that this inducibility is reacquired at the latest stage of DP differentiation as a consequence of positive selection. This could be a mechanism to prevent the activation of DP thymocytes before selection has taken place.

Animals↗
PubMed1994

Teaching family and community dimensions of clinical family medicine in Venezuela.

BACKGROUND AND OBJECTIVES: In Venezuela, family medicine is taught and practiced almost exclusively in ambulatory care settings. This article describes the evolution of the educational strategies that emphasize family and community aspects of clinical practice within one residency program in the country of Venezuela. METHODS: Three distinct phases of development are depicted, beginning with a biomedical and individual-centered approach. Subsequent efforts to involve residents in the community provoked criticism. Resident-faculty dialogue led to modifications and to the success of the current program. Some of the specific educational strategies are: a structured weekly five-hour community afternoon, a 40-hour course titled "Family Dynamics and Counseling," use of the family-oriented home visit to introduce residents to the community aspects of health care, and completion of a community-based and health-related project. RESULTS: A sample of residents and graduates noted an improved doctor-patient relationship, improved ability to work with groups, and improved skills for incorporating preventive medicine with a community focus into their clinical practice. CONCLUSIONS: The community involvement is enthusiastically supported by the residents, as it is perceived as useful for clinical practice. The program prepares family physicians to become more responsive to the health needs and the reality of Venezuelan society.

Community Health Services↗
PubMed1989

Inositol Trisphosphate Metabolism in Carrot (Daucus carota L.) Cells.

The metabolism of exogenously added d-myo-[1-(3)H]inositol 1,4,5-trisphosphate (IP(3)) has been examined in microsomal membrane and soluble fractions of carrot (Daucus carota L.) cells grown in suspension culture. When [(3)H]IP(3) was added to a microsomal membrane fraction, [(3)H]IP(2) was the primary metabolite consisting of approximately 83% of the total recovered [(3)H] by paper electrophoresis. [(3)H]IP was only 6% of the [(3)H] recovered, and 10% of the [(3)H]IP(3) was not further metabolized. In contrast, when [(3)H]IP(3) was added to the soluble fraction, approximately equal amounts of [(3)H]IP(2) and [(3)H]IP were recovered. Ca(2+) (100 micromolar) tended to enhance IP(3) dephosphorylation but inhibited the IP(2) dephosphorylation in the soluble fraction by about 20%. MoO(4) (2-) (1 millimolar) inhibited the dephosphorylation of IP(3) by the microsomal fraction and the dephosphorylation of IP(2) by the soluble fraction. MoO(4) (2-), however, did not inhibit the dephosphorylation of IP(3) by the soluble fraction. Li(+) (10 and 50 millimolar) had no effect on IP(3) metabolism in either the soluble or membrane fraction; however, Li(+) (50 millimolar) inhibited IP(2) dephosphorylation in the soluble fraction about 25%.

Journal Article↗
PubMed1987

myo-Inositol Trisphosphate Mobilizes Calcium from Fusogenic Carrot (Daucus carota L.) Protoplasts.

To determine whether or not inositol trisphosphate (IP(3)) mobilizes calcium in higher plant cells, we investigated the effect of IP(3) on Ca(2+) fluxes in fusogenic carrot (Daucus carota L.) protoplasts. The protoplasts were incubated in (45)Ca(2+)-containing medium and the (45)Ca(2+) associated with the protoplasts was monitored with time. Addition of IP(3) (20 micromolar) caused a 17% net loss of the accumulated (45)Ca(2+) within 4 minutes. There was a reuptake of (45)Ca(2+) and the protoplasts recovered to their initial value by 10 minutes. Phytic acid (IP(6)), also stimulated (45)Ca(2+) efflux from the protoplasts. Both the IP(3(-) ) and the IP(6(-) )induced (45)Ca(2+) efflux were inhibited by the calmodulin antagonist, trifluoperazine.

Journal Article↗