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Biomedical subjects

J Merino

Publications and source records attributed to J Merino.

At least 19 recordsLinked to original sources

Constitutive expression of bcl-2 in B cells causes a lethal form of lupuslike autoimmune disease after induction of neonatal tolerance to H-2b alloantigens.

The bcl-2 protooncogene has been shown to provide a survival signal to self-reactive B cells, but it fails to override their developmental arrest after encounter with antigen. Furthermore, constitutive expression of bcl-2 in B cells does not promote the development of autoimmune disease in most strains of mice, indicating that signals other than those conferred by bcl-2 are required for long-term survival and differentiation of self-reactive B cells in vivo. To further examine the factors that are required for the pathogenesis of autoimmune disease, we have assessed the effect of bcl-2 overexpression on the development of host-versus-graft disease, a self-limited model of systemic autoimmune disease. In this model, injection of spleen cells from (C57BL/6 x BALB/c)F1 hybrid mice into BALB/c newborn parental mice induces immunological tolerance to donor tissues and activation of autoreactive F1 donor B cells through interactions provided by allogeneic host CD4+ T cells. BALB/c newborns injected with spleen cells from (C57BL/6 x BALB/c)F1 mice expressing a bcl-2 transgene in B cells developed high levels of anti-single-stranded DNA and a wide range of pathogenic autoantibodies that were not or barely detectable in mice injected with nontransgenic spleen cells. In mice injected with transgenic B cells, the levels of pathogenic autoantibodies remained high during the course of the study and were associated with long-term persistence of donor B cells, development of a severe autoimmune disease, and accelerated mortality. These results demonstrate that bcl-2 can provide survival signals for the maintenance and differentiation of autoreactive B cells, and suggest that both increased B cell survival and T cell help play critical roles in the development of certain forms of systemic autoimmune disease.

Aging

[Cardiac angiosarcoma].

We report a case of a 29-year-old patient with recurrent hemorrhagic pericardial effusion secondary to a right atrial mass detected by transthoracic echocardiography. A more detailed anatomic study was provided by transesophageal echocardiogram and nuclear magnetic resonance imaging. During surgery, a biopsy confirmed the diagnosis of angiosarcoma. We discuss the contribution of echocardiography and other noninvasive methods to evaluate intracardiac tumors. A brief review of treatment and prognosis is made.

Adult

[Bacteremia caused by Capnocytophaga sp: presentation of 2 cases, one with endocarditis. Review of the literature].

Capnocytophaga sp. is a gram-negative bacilli, scarcely documented as the cause of bacteremias. Two cases of bacteremia caused by Capnocytophaga sp, one of them with endocarditis, are reported here. A review of previous published cases is also presented. One of the patients was immunocompromised, because of chemotherapy, the other, suffered from a rheumatic-cardiopathy which was complicated with endocarditis. Both patients developed an alteration of the oral mucosa. Antibiotic therapy proved to be effective with two patients.

Adult

Value of plasma P-selectin for vascular complications in liver transplantation.

Recent data suggest that plasma P-selectin, an adhesion molecule, may be a clinically useful marker for thrombosis. Hepatic vessel thrombosis is one of the most serious complications following liver transplantation. To assess the contribution of the soluble P-selectin to this complication, we measured plasma P-selectin levels in 32 orthotopic liver transplantations, pre-, intra-, and post-operatively. We found that levels of circulating P-selectin were not different between cirrhotic patients and healthy subjects. Of the 32 patients, 8 had vascular complications. We found a significant increase in the plasma P-selectin concentration in the thrombotic group in early postoperative period compared with the non-thrombotic group (p < 0.002). It measurement may facilitate the diagnosis of thrombosis in the early postoperative period after liver transplantation, and therefore the management of these patients.

Adult

[Importance of HDL cholesterol determination in the evaluation of coronary risk in clinical practice].

OBJECTIVE: To validate to what extent the isolated determination of total Cholesterol (TC) is effective when seeking to predict coronary risk. DESIGN: An observational crossover study of the analytic determinations of the clinics which systematically request TC and HDL-Cholesterol (HDL)--case-finding method. SETTING: Health Centre. PARTICIPANTS: 631 analytic determinations, with samples from people who attended a Health Centre between May and November 1992, were studied. MEASUREMENTS AND MAIN RESULTS: As proof of certainty the Atherogenic Index (AI) was used for the relative risks (RR) of suffering a coronary event in line with the Framingham study. The confidence limits (CL) were calculated to 95% in order to quantify random error and permit comparison. On varying the cut-off points of TC the indicators changed, being more sensitive (S) and less specific (E) with the lower figures: 180 mg/dl, RR > 1, S = 97.5% (CL: 100-94.7) and E = 30.5% (36.8-24.2); RR > 2, S = 100%, E = 22.1% (26.9-17.3) and RR > 3, S = 100%, E = 20.8% (25.3-16.3). As values of TC increase, S diminishes and E increases: 250 mg/dl, RR > 1, S = 48.3% (57.2-39.4), E = 87.2% (91.8-82.6); RR > 2, S = 58.6% (76.5-40.7), E = 77.2% (82-72.4) and RR > 3, S = 63.6% (92-35.2), E = 75.3% (80.1-70.5). CONCLUSIONS: HDL must be determined if TC is -200 mg/dl. If everyone with RR > 2 is to be detected, HDL-cholesterol from TC > or = 180 mg/dl must be measured.

Adult

The ability of B cells to participate in allogeneic cognate T-B cell interactions in vitro depends on the presence of CD4+ T cells during their development.

We have assessed in vitro whether the absence of T cells in the natural environment of F1 hybrid mice influences the ability of their B cells to participate in an allogeneic interaction with CD4+ cells from parental mice. For this purpose, B cells from athymic CB6F1 nu/nu mice or from CB6F1 mice depleted in different T cell subsets were incubated in vitro with purified CD4+ BALB/c cells. Here, we show that B cells from CB6F1 nu/nu mice or from euthymic CB6F1 mice depleted from birth of CD4+ cells were unable to respond to allogeneic stimulation with BALB/c CD4+ T cells, which produce normal levels of cytokines. The addition of dendritic cells from euthymic CB6F1 mice did not revert this defect. B cells from CB6F1 mice lacking CD4+ T cells showed a selective reduction in the expression of CD23. We found a complete restoration of both the CD23 expression and the ability of CB6F1 nu/nu B cells to respond in vitro to an allogeneic stimulation by CD4+ cells in two instances: (1) after neonatal engraftment of a syngeneic thymus into CB6F1 nu/nu mice, which partially reconstitutes the mature T cell populations; and (2) after preincubation of B cells from CB6F1 nu/nu mice with high concentrations of rIL-4. However, the addition of an anti-CD23 mAb did not interfere with the polyclonal activation of CB6F1 B cells in this system. These results indicate that CD4+ cells play an important role in the functional maturation of B cells by promoting their ability to participate in allogeneic cognate T-B cell interactions.

Animals

Circulating adhesion molecules during kidney allograft rejection.

Adhesion molecules appear on leukocytes and endothelial cells mediating the localization and migration of leukocytes to sites of inflammation. Rejecting kidney grafts have shown an increased expression of these molecules. Recent reports have detected in serum soluble forms of adhesion molecules that could play a role in regulating inflammation. We have measured by ELISA the circulating serum levels of ICAM-1, VCAM-1 and E-selectin in: 23 controls, 33 chronic renal failure patients (CRF), 20 hemodialysis patients (HD), 17 samples from 6 patients with stable kidney graft function (STx), 25 samples from 8 patients with steroid-responsive rejection proven by biopsy, and 28 samples from 9 patients with steroid-resistant rejection and good response to OKT3. There was not a rise in cICAM-1 or cE-selectin levels during rejection compared with the steady phase before and after rejection. In the case of cVCAM-1, only the OKT3 group showed increased rejection levels (P < 0.05) that were maintained after rejection. For ICAM-1, CRF and HD groups had higher levels than the remaining groups. cVCAM-1 levels were elevated in all groups when compared with control, furthermore, OKT3 and HD groups had higher levels than the STx, CRF, or steroid-responsive groups. For cE-selectin, we only found differences between the CRF and both rejection groups. Serum creatinine correlated significantly with c-ICAM-1 and cVCAM-1 R = 0.30 and R = 0.22), but not with cE-selectin. We conclude that soluble adhesion molecules levels are not valuable markers for rejection. Patients with chronic renal failure have increased levels of adhesion molecules, which could reflect an impaired elimination.

Antibodies, Monoclonal

[The validity of the separate determination of total cholesterol in the primary prevention of coronary risk].

BACKGROUND: The aim of this study was to validate total cholesterol (TC) determination in the primary prevention of coronary risk and evaluate the prevalence of low HDL cholesterol (HDL-C) levels at the different TC cut-off points to thereby determine the TC level at which HDL-C determination is of interest. METHODS: The atherogenic index was used as the reference method in TC evaluation with the values of low HDL-C levels being evaluated at the following TC cut-off points: 160, 180, 200, 220, 240, 250, and 300 mg/dl (4.44; 4.66; 5.18; 5.70; 6.22; 6.48; 7.77 mmol/l). According to the results of the Framingham study the atherogenic index or the existence of low HDL-C levels were considered as abnormal. The sample included 4,162 workers from the province of Alicante (Spain) selected by consecutive sampling and opportunistic search in January and February, 1993. Validity was calculated with confidence interval of 95%. RESULTS: The atherogenic index was high in 43.7% of the sample, ranging from 6% in the population with TC lower than 160 mg/dl (4.14 mmol/l) to 76.4% in those oscillating between 250-299 mg/dl (6.48-7.76 mmol/l). Low HDL-C levels were detected in 20.1% with a prevalence ranging from 38.8% in those with a TC of less than 160 mg/dl (4.14 mmol/l) to 11.9% in those with TC > or = 250 mg/dl (> or = 6.48 mmol/l). The cut-off points for low TC had high sensitivity (S) and low specificity (SP) (160 mg/dl [4.14 mmol/l]: S = 91.1%, SP = 11.5%; 180 mg/dl [4.66 mmol/l]: S = 95.2%, SP = 30.2%). The highest TC points presented very low S and very high SP (250 mg/dl [6.48 mmol/l]: S = 46.3%, SP = 87.7%; 300 mg/dl [6.48 mmol/l]: S = 7.4%, SP = 97%). CONCLUSIONS: The HDL-cholesterol should be determined in people with a total cholesterol of less than 200 mg/dl (5.18 mmol/l) since, in this group there is an important percentage of individuals with an altered atherogenic index and low HDL-C levels.

Adult

[Diabetes mellitus mortality in Spain: a comparative analysis between Spanish provinces in the period of 1981-1986].

OBJECTIVE: To find and compare mortality because of diabetes mellitus (DM) among the different provinces of Spain in the 1981 to 1986 period. SETTING: The natural movement of population figures of the National Institute of Statistics (INE) and the census of 1981 and register of 1986 were used. DESIGN: A descriptive observation study of a crossover type. Standardisation of rates by the indirect method. Calculation of the ratio of standardised mortality for each province. RESULTS: At the national level, the Communities with an excess of mortality in 1981 were Andalusia, Melilla, the Community of Valencia, Murcia, the Balearics, the Canaries and Extremadura, as well as the provinces of Tarragona, Gerona, Ciudad Real and Albacete. In 1986 the following still had excess of mortality: Andalusia, the Community of Valencia, Murcia, the Balearics, the Canaries, Asturias and Cantabria, along with the provinces of Badajoz and Pontevedra. CONCLUSIONS: The provinces with an excess mortality because of diabetes mellitus are geographically grouped (with some exceptions) in the south and south-east of Spain and the island communities.

Adult

Therapeutic effect of early thymic irradiation in (NZB x NZW)F1 mice, associated with a selective decrease in the levels of IgG3 and gp70-anti-gp70 immune complexes.

The lupus-prone (NZB x NZW)F1 female mice (NZB/W) develop an autoimmune disease characterized by production of autoAb and fatal glomerulonephritis. Since it has been previously shown that total lymphoid irradiation has a beneficial effect in this model, we have analyzed whether early thymic irradiation (ETI) could improve the course of the lupus-like syndrome in these mice. NZB/W mice received thymic irradiation (4500 rads) beginning at 10 weeks of age, prior to the onset of autoimmune manifestations. Then, they were evaluated for survival, renal histology, and serological markers of autoimmunity, in comparison to nonirradiated NZB/W females. The treatment with ETI improved nephritis and survival in NZB/W mice: 50% mortality was observed at 12 months in irradiated mice and at 9 months in untreated mice. This improved survival could not be attributed to a reduction in the titers of anti-dsDNA Ab nor in the levels of total immune complexes which were essentially identical in both groups. By contrast, this improvement was related to a selective normalization in the serum levels of IgG3 and gp70-anti-gp70 immune complexes (gp70IC) in ETI NZB/W female mice as compared to that seen in nonirradiated NZB/W females. These data show the therapeutical effect of ETI and support the pathogenic role of IgG3 and gp70IC in the development of glomerulonephritis in NZB/W mice.

Animals

[Opinion of university professors on the suitability of specific primary care training in medical students].

OBJECTIVE: To find the opinion of teachers at the University of Alicante about the appropriateness of a Primary Care Theory-Practice programme within the Medicine curriculum. DESIGN: A descriptive observation study of a crossover nature. SETTING: Teachers of the Departments of Medicine and Public Health who had had contact with the Primary Care Theory-Practice programme. PARTICIPANTS: 44 out of 71 teachers (62%) replied. INTERVENTION: An 11-question survey was answered anonymously between October 1993 and June 1994. MEASUREMENTS AND MAIN RESULTS: 77.3% (95% Confidence Interval 64.9-89.7%) considered appropriate the theoretical content at undergraduate level, where there was an average 18.5 hours teaching (C.I. 15.8-21.2); and 95.5% (C.I.89.4-100%), the practicals at a Health Centre, where there was an average 65.2 hours (C.I. 43.1-87.3) work. 43.9% thought it was appropriate to form a separate subject and 39% favored integrating these themes into other subjects. Theoretical contents would be basically teaching general information about Primary Care; and practical work would be clinical activities. The greatest advantages regarding carrying out practical work in Health Centres were: the student finds pathology more prevalent and learns to provide practical answers. The greatest disadvantages were: the low methodological knowledge and teaching preparation of the Teams. CONCLUSIONS: Those interviewed considered that the teaching at undergraduate level of a Primary Care subject with theoretical-practical content would be useful. The advantages, its contents and some difficulties were noted.

Aged

CD4+ T cells determine the ability of spleen cells from F1 hybrid mice to induce neonatal tolerance to alloantigens and autoimmunity in parental mice.

Spleen cells from F1 hybrid mice injected into newborn parental mice induce a state of cytolytic unresponsiveness to the corresponding alloantigens. However, these mice develop a transient autoimmune syndrome characterized by the production of multiple autoantibodies and glomerulonephritis. Previous reports indicated that the depletion of F1 donor T cells, shortly prior the injection into parental mice, does not interfere with any of these events. Here, we have explored whether the continuous absence of T cells in F1 mice influences the ability of their spleen cells to induce neonatal tolerance to alloantigens and the associated autoimmune manifestations. Our results revealed that spleen cells from athymic (BALB/c x C57BL/6) F1 hybrid (CB6F1) nu/nu mice or from euthymic CB6F1 mice depleted from birth of CD4+ T cells, but not of CD8+ T cells, are unable to induce neonatal tolerance to alloantigens and autoimmune manifestations. By contrast, the partial reconstitution of T cells in CB6F1 nu/nu mice, after the neonatal graft of a syngeneic thymus, restored the capacity of spleen cells from these mice to induce tolerance and autoimmunity when injected into newborn BALB/c mice. These results demonstrate that the functional defect of spleen cells from athymic CB6F1 nu/nu mice to induce neonatal tolerance to alloantigens is directly related to the long-term absence of mature CD4+ T cells. Interestingly, a new increase in the titers of anti-DNA Ab was observed when spleen cells from athymic CB6F1 nu/nu mice were injected into adult BALB/c mice that had been tolerized at birth with normal CB6F1 spleen cells. This finding indicates that B cells from CB6F1 nu/nu mice recover their capacity to interact with alloreactive Th2 cells when they are placed into mice having functional CD4+ T cells. These data indicate that the continuous absence of CD4+ T cells causes a reversible functional defect in F1 spleen cells that determines their inability to induce neonatal tolerance and autoimmunity.

Animals

Effect of long-term anti-CD4 or anti-CD8 treatment on the development of lpr CD4- CD8- double negative T cells and of the autoimmune syndrome in MRL-lpr/lpr mice.

We have determined the effect of anti-CD4 or anti-CD8 monoclonal antibody (mAb) treatment from birth on the generation of the lpr CD4- CD8- double-negative (DN) T cell subset and on the development of lupus-like autoimmune syndrome in MRL-lpr/lpr mice. Both anti-CD4 and anti-CD8 mAb treatments resulted in a marked inhibition of lymph-adenopathy, whereas the development of the lpr DN T cells and of the lupus-like autoimmune syndrome strikingly differed in these two groups of mice. The treatment with anti-CD8 mAb almost completely blocked the appearance of the lpr DN T cells without any significant effect on the development of lupus-like autoimmune syndrome in MRL-lpr/lpr mice. In contrast, mice treated with anti-CD4 mAb failed to develop a lupus-like syndrome, while they still developed the lpr DN T cell subset, the predominant population in their lymph nodes, although absolute numbers were markedly diminished. Our results support the idea that CD8+ T cells are a major source of the lpr DN T cells, and that the lpr DN T cells play a minor, if any, role in the pathogenesis of lupus-like autoimmune syndrome in MRL-lpr/lpr mice.

Animals

Brain maturation estimation using neural classifier.

Quantitative electroencephalographic (EEG) signal analysis has revealed itself as an important diagnostic tool in the last few years. Through the use of signal processing techniques, new quantitative representations of EEG data are obtained. To automate the diagnosis, a problem of supervised classification must be solved on these. Artificial Neural Networks provide an alternative to more traditional classifier systems for this task. The objective of this paper is to perform a comparison between several classifiers in a particular problem, the brain maturation prediction. The data preprocessing/feature extraction process and the methodology for making the comparison are described. Performance of the methods is evaluated in terms of estimated percentage of correctly classified subjects.

Adolescent

[The usefulness of different markers in the diagnosis of advanced HIV infection].

BACKGROUND: The aim of this study was to evaluate the usefulness of different markers to diagnose advanced infection by the human immunodeficiency virus (HIV) (AIDS or CD4 lymphocyte < 0.2 x 10(9)/L), establish the degree of correlation and define markers of advanced infection in primary health care. METHODS: Clinical, hematological, biochemical, cellular, serological and immunological variables were analyzed in 146 patients diagnosed for the first time with HIV infection. The patients were classified into three stages: A (II, III, CDC-1987), B (IV-A, IV-C2) and C or advanced (IV-C1, IV-D). The following data were compared: the results in the three stages, the degree of correlation, the specificity and sensitivity to the diagnosis of AIDS. Two multiple logistic regression models were established: the first for all the variables and the second for only those available in primary health care. RESULTS: All the markers except the triglycerides, IgG, IgM, and beta 2-microglobulin presented significant differences in the stages (p < 0.05). With the exception of the CD3+, CD4+ and CD8+ lymphocytes (r > or = 0.6 or -0.6) the remaining variables were independent. The decrease in CD4+ and the increase in neopterin were very sensitive markers (> 95%) but only hyperamylasemia demonstrated a specificity greater than 95% for the diagnosis of advanced infection. Oropharyngeal candidiasis (OR = 4.80) and the CD4+ lymphocyte (OR = 0.99) had the greatest weight in the first model. In the second model the most significant markers were weight loss (OR = 4.41), a decrease in lymphocytes (OR = 7.65) and an increase in IgA (OR = 5.82) with p < 0.01 and a predictive value of 85.16%. CONCLUSIONS: The presence of weight loss, lymphocyte count < 1 x 10(9)/L and an increase in IgA may be used in primary health care to diagnose advanced infection by the human immunodeficiency virus. Asymptomatic hyperamylasemia with no apparent cause suggests advanced infection.

Acquired Immunodeficiency Syndrome

[Validity of 6 indirect methods to assess treatment compliance in arterial hypertension].

BACKGROUND: For adequate control of high blood pressure (HBP) the therapy indicated must be correct, with effective medication which must be taken as required. At a collective level methods to evaluate patients' compliance of the above are necessary since without the same the efficacy of the drugs cannot be determined. In this study methods allowing the clinic to easily quantify patient fulfillment were sought. METHODS: Six indirect methods were used to evaluate therapeutic compliance: 1) self communicated compliance (SC), 2) appointment attendance (AA), 3) degree el control obtained in the blood pressure (DC), 4) Morinsky and Green tests (M-G), 5) patient's knowledge of the disease (PK) and 6) doctor's judgement on patient's compliance (DJ). All the above were applied to 152 hypertense patients randomly selected from the Health Centers of Alfaz and Alicante (Spain). Concordance with the compliance obtained from the "counting of tablets" in the patient's home and by surprise were evaluated by double entry tables. RESULTS: The SC is the method which obtains greatest specificity (96.7%), exactness (73%), probability of low compliance (88%) and percent of probability of low compliance (11.3%). The PK had greatest sensitivity (83.3%) and greater probability of high compliance (83.6%) and percentage of probability of high compliance (0.3%). The SC (23.1%), AA (1.3%) and the DJ (7.5%), overestimate good compliance. The M-G test (7.9%) and the PK (20.4%) overestimate had compliance. CONCLUSIONS: In this study self communicated compliance and patient's knowledge of disease were the methods which provided the best indicators of validity to measure therapeutic compliance in high blood pressure in outpatients, although there is the inconvenience of significantly over and under estimating good and bad compliance.

Evaluation Studies as Topic