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Biomedical subjects

J Merino

Publications and source records attributed to J Merino.

At least 37 records · Page 2Linked to original sources
PubMed1999

Cytokine flow cytometry differentiates the clinical status of multiple sclerosis (MS) patients.

In this study we have examined intracellular cytokines in peripheral blood mononuclear cells (PBMC) of MS patients by flow cytometry (cytokine flow cytometry). MS progressive patients showed an increased number of cells producing interferon-gamma (IFN-gamma) after activation with phorbol 12-myristate 13-acetate and ionomycin, compared with patients with clinically inactive forms (P < 0001) and with healthy controls (P = 0001). These cells belonged to the CD4+ and CD8+ subsets in similar proportions. Clinically inactive patients showed a lower level of cells producing IL-2 than controls (P = 0.03) and active MS patients (P = 0.03). Most IL-2-producing cells were CD4+ lymphocytes, although a small part of the IL-2 was also produced by CD8+ cells. The percentage of cells producing simultaneously IL-2 and IFN-gamma was increased in active MS and they were mainly CD4+ lymphocytes. No differences in the production of IL-4 were observed between groups. However, we found an increased IL-10 production in clinically active MS patients (P = 0.03). Treatment with IFN-beta of active MS patients showed lower levels of cytokines when compared with untreated MS patients. This methodological approach could help in the follow up and therapeutic monitoring of MS patients.

Adult↗
PubMed1999

Different roles for LFA-1 and VLA-4 integrins in T-B-cell interactions in vivo.

Adhesion molecules are critical in the cellular interactions involved in specific immune responses. They are used for homing, cell migration, cell-cell contact and, in some cases, for the delivery of costimulatory signals. Since the host-versus-graft (HVG) reaction represents a particular form of T-B-cell interaction, we have explored whether the inhibition of lymphocyte function-associated antigen-1/intracellular adhesion molecule-1 (LFA-1/ICAM-1) interactions and the signalling through very late activation antigen-4 (VLA-4) have any effect on the development of a lupus-like disease in BALB/c mice injected at birth with (BALB/cxC57BL/6)F1 spleen cells. In close association with the development of tolerance to donor allografts, these mice show a polyclonal activation of F1 donor B cells by alloreactive host CD4+ T cells, manifested by the production of autoantibodies (autoAbs) and the development of a mild glomerulonephritis. The dose of the monoclonal antibody (mAb) employed has been adjusted to block completely the molecule on the surface of peripheral lymphocytes without interfering with the induction of neonatal tolerance. Injection of saturating doses (100 microg/2 days) of either anti-LFA-1alpha or anti-ICAM-1 mAbs, but not anti-VLA-4alpha or anti-LFA-1beta mAbs, blocks the production of anti-ssDNA autoAbs and the thrombocytopenia characteristic of this HVG disease (HVGD). However, anti-VLA-4alpha treatment is only able to delay the production of autoAbs and the anti-LFA-1beta treatment, not to modify the evolution of the HVGD. These results point to the relevance of LFA-1/ICAM-1 interactions, but not of the VLA-4-mediated signal, in the polyclonal B-cell activation occurring during the allogeneic interactions between host T helper type 2 cells and donor B cells in HVGD.

Animals↗
PubMed1998

Diva, a Bcl-2 homologue that binds directly to Apaf-1 and induces BH3-independent cell death.

We have identified and characterized Diva, which is a novel regulator of apoptosis. Sequence analysis revealed that Diva is a member of the Bcl-2 family of proteins containing Bcl-2 homology domain 1, 2, 3, and 4 (BH1, BH2, BH3, and BH4) regions and a carboxyl-terminal hydrophobic domain. The expression of Diva mRNA was detected in multiple embryonic tissues but was restricted to the ovary and testis in adult mice. The expression of Diva promoted the death of 293T, Ramsey, and T47D cells as well as that of primary sensory neurons, indicating that Diva is a proapoptotic protein. Significantly, Diva lacks critical residues in the conserved BH3 region that mediate the interaction between BH3-containing proapoptotic Bcl-2 homologues and their prosurvival binding partners. Consistent with this, Diva did not bind to cellular Bcl-2 family members including Bcl-2, Bcl-XL, Bcl-w, Mcl-1, and A1/Bfl-1. Furthermore, mutants of Diva lacking the BH3 region fully retained their proapoptotic activity, confirming that Diva promotes apoptosis in a BH3-independent manner. Significantly, Diva interacted with a viral Bcl-2 homologue (vBcl-2) encoded by the Kaposi's sarcoma-associated herpesvirus. Consistent with these associations, apoptosis induced by Diva was inhibited by vBcl-2 but not by Bcl-XL. Importantly, Diva interacted with Apaf-1, an adapter molecule that activates caspase-9, a central death protease of the apoptotic pathway. The expression of Diva inhibited the binding of Bcl-XL to Apaf-1, as determined by immunoprecipitation assays. Thus, Diva represents a novel type of proapoptotic Bcl-2 homologue that promotes apoptosis independently of the BH3 region through direct binding to Apaf-1, thus preventing Bcl-XL from binding to the caspase-9 regulator Apaf-1.

Amino Acid Sequence↗
PubMed1998

[Relationship between medical treatment compliance and the degree of control in patients with high blood pressure, non-insulin dependent diabetes mellitus and dyslipidemia].

BACKGROUND: To study the relationship between therapeutic compliance and the control of arterial hypertension, non insulin dependent diabetes mellitus and hyperlipidemia. PATIENTS AND METHODS: Prospective study performed on 174 hypertensive patients, 107 with diabetes and 107 with hyperlipidemia evaluating compliance by counting of tablets in two home visits. RESULTS: 34% hypertensive patients, 20% diabetics and 37% hyperlipidemics that took medication as instructed or more than they should were badly controlled. CONCLUSIONS: The control grade of high blood pressure, non insulin dependent diabetes mellitus and hyperlipidemia not only depends on improving compliance but also in adapting pharmacologic prescriptions.

Aged↗
PubMed1998

[Factors involved in the non-compliance of the pharmacologic treatment of dyslipidemia].

OBJECTIVES: To find how much non-compliance with lipid-lowering drug treatment there is, its causes and to describe the profile of non-compliant patients. DESIGN: Prospective study. SETTING: Primary Care Centres in the province of Alicante. PATIENTS: 107 patients under drugs treatment for lipaemic disorders and belonging to live General Medical practices. MEASUREMENTS AND MAIN RESULTS: To evaluate compliance, the method of a surprise count of pills in the patient's home was used. Compliant patients were defined as those with between 80 and 110% compliance. 46.7% were non-compliant (C.I. 37.3-56.2), with 42% under-compliant and 4.7% over. Forgetfulness and unawareness accounted for 68% of the reasons for non-compliance. Associated factors were: moderate to high cardiovascular risk (p = 0.03), stating that the drug treatment was followed badly (p = 0.01), less than a year in regular treatment (p = 0.006), monitoring lipaemia poorly (p = 0.003). CONCLUSIONS: Non-compliance with pharmacological treatment in patients with lipaemia is high. Its causes are known, as are several factors associated to non-compliance which could be used to identify the non-complier.

Aged↗
PubMed1998

Mtd, a novel Bcl-2 family member activates apoptosis in the absence of heterodimerization with Bcl-2 and Bcl-XL.

We have identified and characterized Mtd, a novel regulator of apoptosis. Sequence analysis revealed that Mtd is a member of the Bcl-2 family of proteins containing conserved BH1, BH2, BH3, and BH4 regions and a carboxyl-terminal hydrophobic domain. In adult tissues, Mtd mRNA was predominantly detected in the brain, liver, and lymphoid tissues, while in the embryo Mtd mRNA was detected in the liver, thymus, lung, and intestinal epithelium. Expression of Mtd promoted the death of primary sensory neurons, 293T cells and HeLa cells, indicating that Mtd is a proapoptotic protein. Unlike all other known death agonists of the Bcl-2 family, Mtd did not bind significantly to the survival-promoting proteins Bcl-2 or Bcl-XL. Furthermore, apoptosis induced by Mtd was not inhibited by Bcl-2 or Bcl-XL. A Mtd mutant with glutamine substitutions of highly conserved amino acids in the BH3 domain retained its ability to promote apoptosis, further indicating that Mtd does not promote apoptosis by heterodimerizing with Bcl-2 or Bcl-XL. Mtd-induced apoptosis was not blocked by broad range synthetic caspase inhibitors z-VAD-fmk or a viral protein CrmA. Mtd is the first example of a naturally occurring Bcl-2 family member that can activate apoptosis independently of heterodimerization with survival-promoting Bcl-2 and Bcl-XL.

Amino Acid Sequence↗
PubMed1998

Progressive decrease of CD8high+ CD28+ CD57- cells with ageing.

An age-dependent decrease in T cell responsiveness to CD28 costimulation has been described. In order to test the hypothesis that an age-related decrease in CD28 expression by CD8+ T lymphocytes might be involved, we analysed 67 healthy donors ranging in age from 15 to 69 years for their CD8+ T cell expression of CD28 and CD57. We found a statistically significant decrease of CD28 expression through ageing and a significant increase of CD57 expression, both markers being mutually exclusive. Given that cytomegalovirus (CMV) is reported to induce CD57 expression, and since the carrier status for this ubiquitous virus increases with age in the general population, it seemed essential to evaluate whether the phenotypic age-related changes described in CD8high+ cells were not influenced by the CMV carrier status of the individuals. Accordingly, we performed a multivariate analysis to assess the independent association of age and CMV carrier status with CD28 and CD57 expression in CD8high+ cells. Results showed that the progressive decrease in CD8high+ CD28+ CD57- cells was associated only with age, while the expansion of the CD8high+ CD28- CD57+ subset depended both on age and CMV, although mainly on age. We conclude that ageing is accompanied by a progressive loss of CD28 expression in CD8+ T cells and a reciprocal enhancement of CD57 expression, both facts being probably related to the repeated antigenic stimulation occurring throughout life.

Adolescent↗
PubMed1998

Host H-2 haplotype modulates the induction of host-versus-graft disease after the induction of neonatal tolerance to H-2 alloantigens.

Mice injected at birth with semiallogeneic spleen cells develop a host-versus-graft disease (HVGD) characterized by the polyclonal activation of donor B cells by alloreactive host CD4+ T cells, the production of autoantibodies (autoAb) and the development of an inmmunocomplex-mediated glomerulonephritis. It has been demonstrated that the recognition of MHC class II, but not class I or non MHC, alloantigens triggers the development of the autoimmune syndrome (AIS). The finding of different expression patterns of Ia molecules in different mouse strains, and a closed restriction of some immune responses to particular H-2 haplotypes, prompted us to analyze whether variations in the expressed MHC class II molecules modify the HVGD. First, newborn BALB/c mice received spleen cells from F1 hybrid mice obtained by mating BALB/c mice with several mouse strains differing in the H-2 haplotype. Second, spleen cells from different F1 mice were neonatally injected in mice of both parental strains. All groups of BALB/c mice injected with different combinations of F1 mice showed an HVGD with a very similar serological course. However, in some instances, duration was different when comparing both parental strains injected with spleen cells from the mutual F1 hybrids. These results suggest that host MHC, but not donor MHC haplotype may modulate the AIS associated with the induction of neonatal tolerance.

Animals↗
PubMed1998

Regulation of B cell apoptosis by Bcl-2 and Bcl-XL and its role in the development of autoimmune diseases (Review).

Cell death is a common event during B cell development. The demise of developing B cells is a regulated process that serves to select cell populations bearing functional receptors and to remove cells that are no longer needed or potentially autoreactive. Bcl-2 and Bcl-XL, two members of the bcl-2 gene family of programmed cell death regulators with anti-apoptotic activity, are expressed in a highly regulated pattern during B cell maturation. Overexpression of Bcl-2 in developing B cells of transgenic mice, in the presence of T cell dependent costimulatory signals, results in the generation of a modified B cell repertoire and in the production of pathogenic autoantibodies. While disregulation of programmed cell death in B cells may cause autoimmune manifestations in mice, the involvement of such alterations in the pathogenesis of autoimmune diseases in humans merits further investigation.

Animals↗
PubMed1997

[Factors involved in noncompliance with drug treatment in non-insulin dependent diabetes mellitus].

OBJECTIVE: To find the level of non-compliance with treatment with oral hypoglycemics, its causes and the profile of non-compliant patients. DESIGN: Prospective study. SETTING: Primary Care Centres in the province of Alicante. PATIENTS: 107 diabetics not dependent on insulin on the lists of five General Medicine practices and all receiving pharmacological treatment. MEASUREMENTS AND MAIN RESULTS: The method used to value compliance was a surprise count of pills in the patient's home. Patients achieving 80-110% compliance were considered compliant. The level of non-compliance was 51.5% (C.I. 42.1%-61%), 36.5% being hypocompliers and 15% hypercompliers. Forgetting (40.7%) and lack of knowledge (29.5%) were the most frequent reasons for non-compliance. The factors associated with non-compliance were: over four years evolution of the disease (p = 0.02), the diet not properly observed (p = 0.03), over a year in regular treatment (p = 0.006), poor control of the disease valued by HbA1C (p = 0.003). CONCLUSIONS: A high level of non-compliance with pharmacological treatment was found for patients with Diabetes Mellitus not dependent on insulin. Its causes were identified and factors associated with poor compliance were profiled.

Aged↗
PubMed1997

[Factors involved in noncompliance with pharmacological treatment in arterial hypertension].

OBJECTIVES: To find the amount of non-compliance with medical treatment for Hypertension and its causes, and to describe the profile of non-compliant patients. DESIGN: A crossover study performed on two home visits. SETTING: A rural Health Centre at Calpe, Alicante. PATIENTS: The sample was obtained from the census of medically treated hypertense patients. 174 of the 200 patients chosen completed the study. MEASUREMENTS AND MAIN RESULTS: Compliance was evaluated by a surprise count of pills in the patient's home. Patients complying between 80 and 110% were considered compliant. There was 47.7% non-compliance (C.I. 95%: 40.3-55.1), with 31% under-compliers and 16.7% over-compliers. Lack of information (39.8%) and forgetfulness (28.9%) were the most common causes of non-compliance. CONCLUSIONS: A high amount of non-compliance was shown, including an important number of over-compliers. Its causes were defined along with other reasons predicting non-compliance.

Age Factors↗
PubMed1997

[The relationship between primary and specialized care].

OBJECTIVES: To find the current situation regarding the relationship between Primary Care and specialist doctors. To find the defects in this relationship and to propose actions to improve the situation. DESIGN: Delphi technique. SETTING: Area Medical Directors, Medical Coordinators of Primary Care Centres, Hospital Medical Directors, Internal Medicine Service chiefs and Casualty directors from the entire Community of Valencia. RESULTS: After a qualitative analysis of the replies given in the first and second questionnaires, the 10 most serious problems for the Primary Care/Hospital relationship were extracted, along with 10 possible solutions to improve this relationship. CONCLUSIONS: The main problems detected between Hospital and Primary Care concerned the professional and organisational areas. The solutions suggested mainly centered on the organisational area. Specific differences were found in the prioritization of the replies, both for problems and solutions, depending on whether the point of view was Primary or Hospital Care.

Community Health Centers↗
PubMed1997

[The validity of 6 indirect methods for assessing compliance with pharmacological treatment in dyslipidemias].

OBJECTIVE: To validate six indirect methods of identifying patients who do not comply with their treatment with hypolipaemiant drugs. DESIGN: A prospective study. SETTING: Primary care centres in the province of Alicante. PATIENTS: 107 lipaemic patients, on the lists of 5 General Medical practices and on drugs treatment. MEASUREMENTS AND MAIN RESULTS: The most accurate way to assess compliance was the surprise counting of pills in patients' homes. Patients who had between 80 and 110% compliance were defined as compliant. The six indirect methods validated were: Communication of self-compliance (CS), Attendance at appointments (AA), Doctor's judgment (DJ), Information about the illness (II), the Morisky-Green test (MG) and the grade of control (GC). AA, DJ and CS were the methods with highest specificity (91.2%-89.5%). GC and II were the most sensitive (88%-82%). GC obtained the greatest negative predictive value (77.7%), and DJ the greatest positive predictive value (73.6%). The concordance index (kappa) ranged from 0.23 for GC and -0.002 for II. CONCLUSIONS: GC, DJ and CS are the methods with the best validity indicators and concordance. They could, therefore, be used together in clinical practice to identify patients not complying with their hypolipemiant treatment.

Humans↗
PubMed1997

[The validity of 6 indirect methods for assessing drug treatment compliance in arterial hypertension].

OBJECTIVE: To validate six indirect methods, which were simple and easy to apply in clinical practice, of identifying patients who did not comply with drugs treatment for hypertension. DESIGN: A prospective study based on two visits to patient's home. SETTING: rural health centre at Calpe, Alicante. PATIENTS: 174 patients (58 men and 116 women) were included. They were chosen at random from the centre's records of hypertense patients. MEASUREMENTS AND MAIN RESULTS: Compliance was assessed by the method of a surprise counting of pills in the patient's home. Patients who had between 80 and 110% compliance were defined as compliant. The six indirect methods validated were: communication of self-compliance (CS), attendance at appointments (AA), doctor's judgment (DJ), information about the illness (II), hypertension control (HC) and the Morisky-Green test (MG). II was the most sensitive (81.9%). CS reached the highest specificity (93.4%), the best positive predictive value (81.8%) and the best concordance index (kappa, 0.26). CONCLUSIONS: II and CS are the indirect methods with the best validity indicators and could be used together to assess compliance with drugs treatment for hypertension.

Aged↗