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Biomedical subjects

E Munoz

Publications and source records attributed to E Munoz.

9 recordsLinked to original sources

IL-4 and IL-2 selectively rescue Th cell subsets from glucocorticoid-induced apoptosis.

It is well established that T cell maturation and activation are negatively regulated by a mechanism termed apoptosis. We now present evidence that glucocorticoids, known to possess immunosuppressive properties, cause apoptosis in mature Th cells, similarly to what has been reported for thymocytes. Th cells treated with the synthetic glucocorticoid dexamethasone show genome fragmentation into oligonucleosomal fragments, and proliferation of growth factor stimulated Th cells is inhibited by glucocorticoids. We show that IL-4 specifically rescues Th2 cells from dexamethasone-mediated apoptosis, whereas IL-2 and IL-1 are ineffective in these cells. However, IL-2 is the relevant rescue-factor of glucocorticoid-treated Th1 cells. The rescue induced by IL-4 and IL-2 is thought to be mediated by protein kinases (possibly protein kinase C), as evidenced by the fact that the protein kinase inhibitor H7 blocks the action of IL-4 and IL-2 in glucocorticoid-treated cells. Our in vitro data show that mature T cells can be protected by their own growth factors from the deleterious effects of the synthetic glucocorticoid dexamethasone, and suggest that specific interactions occur between lymphokines and naturally produced glucocorticoids in vivo, which may play a role in the regulation of the immune response.

Cell Death

Hospitalisation patterns in children from 10 aboriginal communities in the Northern Territory.

OBJECTIVE: To describe childhood hospitalisation patterns in rural Aboriginal communities in the Northern Territory. DESIGN: Longitudinal data for 1976-1985 were collected retrospectively between March 1986 and December 1987. COHORT: All children born between 1 January 1976 and 31 December 1985 and identified in records at 10 community health centres were included in the study, except for 30 children who were residents of more than one community. Records of hospital admissions were ascertained for the remaining 2254 children until five years of age or 31 December 1985, whichever was earlier. RESULTS: Mean admission rates for Aboriginal children aged 0-1 year were two to three times the national average, and there was a fourfold excess in the number of days in hospital and the number of deaths before the age of five years for Aboriginal infants. Admission rates varied by community, age, year and sex: at 0-6 months of age, rates for communities ranged from a minimum of 0.21 to a maximum of 1.46 admissions per child-year at risk and mean rates increased from 0.50 per year in 1976 to 1.05 in 1985; mean admission rates declined from 0.84 per child-year at age 0-6 months to 0.12 at age 37-60 months. Boys were admitted to hospital more frequently than girls. For communities, hospital stay ranged from a minimum of 2.7 to a maximum of 15.3 hospital days per child-year at risk. CONCLUSIONS: Differences of up to sevenfold in hospitalisation rates between communities highlight the potential for primary and secondary prevention of childhood disease in Aboriginal communities.

Anemia

Social and environmental factors in 10 aboriginal communities in the Northern Territory: relationship to hospital admissions of children.

OBJECTIVE: To identify social and environmental differences associated with differences in admission rates of children from 10 rural Aboriginal communities in the Northern Territory. DESIGN: Between March 1986 and December 1987, records of hospital admissions of the cohort of children for 1976-1985 were examined retrospectively; cross-sectional measurements of 74 historical, social and environmental characteristics of each community were collected. SAMPLE: All 1961 children born between 1 January 1976 and 31 December 1985 and still living in the 10 communities. METHOD: Scores on social and environmental factors for each community were generated by factor analysis. Generalised linear interactive modelling was used to investigate the association between these scores and admission rates. RESULTS: Mean admissions per child-year at risk were higher in Central Australian communities (range, 0.41-0.93) than Top End communities (0.26-0.38). Factor I accounted for 30% of the social and environmental differences between communities: communities with a high score on this factor had more houses, fewer shared toilets, more electrical appliances, better personal hygiene and a history of mission administration. High scores on this factor were predictive of lower admission rates and the factor explained most of the differences in admission rates between the Top End and Central Australian communities. Factor VI, correlated with dilapidated dwellings and fewer Aboriginal Health Workers, explained some differences in admission rates between six Top End communities. CONCLUSIONS: Social and environmental factors correlated with the degree of community development are associated with the health of Aboriginal children. Improved development programs should be community-controlled and evaluated to identify the social, educational, behavioural and environmental changes that are most effective in improving health.

Child, Preschool

Bioavailability of energy, nitrogen, fat, zinc, iron and calcium from rural and urban Mexican diets.

The availabilities of nutrients from a representative rural Mexican diet (RMD) and a representative urban Mexican diet (UMD) were evaluated by balance experiments in sixteen Mexican women. Compared with UMD, the plant-based RMD led to a higher number of defaecations and higher faecal excretion of dry matter, fat, nitrogen and energy. Apparent digestibility of N from RMD was only 67% compared with 90% from UMD. N balance was 0.4 and 2.6 g/d with RMD and UMD respectively (P < 0.001). Apparent digestibility of energy was 89 and 95% from RMD and UMD respectively (P < 0.001). Calculation of the metabolizable energy (ME) using Atwater's (Atwater & Bryant, 1900) general factors overestimates the determined ME in RMD by 8%. The Food and Agriculture Organization/World Health Organization/United Nations University (World Health Organization, 1985) recommended factors for correction of digestibility of fibre intake overestimate energy and protein absorption from RMD. The diets provided similar amounts of zinc, and its apparent absorption from RMD was 0.5 mg/d (4.6%) and its balance was 0.1 mg/d. This compared with values for UMD of 1.6 mg/d (16%) and 1.2 mg/d respectively. Iron intake was higher from RMD (17.4 v. 11.6 mg/d; P < 0.01), but apparent absorption was 17 v. 35% and balance was 2.7 and 3.8 mg/d (P < 0.001) for RMD and UMD respectively. RMD also contained more calcium (745 v. 410 mg/d) but apparent absorption from RMD was negative (-136 v. 15 mg/d) and balance was more negative (-197 v. -77 mg/d; P < 0.05). Thus, the content of these minerals is not low in the rural diet but their bioavailabilities are poor.

Adolescent

Inhibition of dipeptidyl aminopeptidase IV (DP-IV) by Xaa-boroPro dipeptides and use of these inhibitors to examine the role of DP-IV in T-cell function.

Dipeptidyl peptidase IV (DP-IV; dipeptidyl-peptide hydrolase, EC 3.4.14.5) is a serine protease with a specificity for cleaving Xaa-Pro dipeptides from polypeptides and proteins. It is found in a variety of mammalian cells and tissues, including those of lymphoid origin where it is found specifically on the surface of CD4+ T cells. Although the functional significance of this enzyme has not been established, a role in T-cell activation and immune regulation has been proposed. Here we report that Ala-boroPro and Pro-boroPro, where boroPro is the alpha-amino boronic acid analog of proline, are potent and specific inhibitors of DP-IV, having Ki values in the nanomolar range. Blocking the N terminus of Ala-boroPro abolishes the affinity of this inhibitor for DP-IV, while removal of the N-terminal residue, to give boroPro, reduces the affinity for DP-IV by 5 orders of magnitude. The dipeptide boronic acids exhibit slow-binding kinetics, while boroPro does not. We also report here that low concentrations of Pro-boroPro inhibit antigen-induced proliferation and interleukin 2 production in murine T-cell lines but do not inhibit the response of these T cells to the mitogen concanavalin A. These results indicate that DP-IV plays a role in antigen-induced, but not mitogen-induced, activation of T lymphocytes.

Animals

Familial transmission of a 3q;22p translocation, with partial trisomy of chromosome 3 in the propositus.

A family, carrying a balanced 3q;22p translocation, was detected through a propositus who showed multiple congenital malformations. As there are no previous references of similar cases where identification techniques were performed, the authors present this material for consideration in the delineation of clinical syndromes associated with specific chromosomal anomalies.

Abnormalities, Multiple

Long-term results in diabetic patients undergoing heart transplantation.

We conducted a retrospective study of 305 nondiabetic patients and 37 diabetic patients who underwent heart transplantation from July 1982 to May 1990. Actuarial survival was similar for both groups of patients at 1 year (76.4% versus 81.3%) and at 2 years (69.6% versus 73.0%). Because we were interested in long-term results, we further analyzed only those patients surviving more than 1 year after transplantation (214 nondiabetic patients and 29 diabetic patients). Mean follow-up for the nondiabetic patients was 31.8 +/- 16.2 months and for the diabetic patients, 32.9 +/- 4.1 months. The respective mean age in each group was 50.4 +/- 10.3 years and 51.6 +/- 9.1 years. No difference was observed between the nondiabetic patients and diabetic patients regarding the rejection rate per patient-month (0.040 +/- 0.041 versus 0.045 +/- 0.051 episodes per patient-month), the infection rate per patient-month (0.056 +/- 0.081 versus 0.081 +/- 0.102 episodes per patient-month), or renal function as evidenced by mean creatinine levels at 1, 2, and 3 years. Twelve patients were insulin-dependent before transplantation; and 1 year after transplantation, they required an insulin dose 2.12 times greater than the dose before operation. Coronary artery disease developed in 32.8% of the nondiabetic patients, compared with 31.0% of the diabetic patients by the fourth year of follow-up. Despite the need for increased insulin doses, the diabetic patients had similar long-term survival to that of the nondiabetic patients, without an increased risk of rejection, infection, renal dysfunction, or coronary artery disease. Our experience supports the feasibility of heart transplantation in selected diabetic recipients.

Adult

Quality of life in long-term survivors of the Hemopump left ventricular assist device.

The courses of 10 patients (nine men and one woman; mean age, 54 years) were reviewed to determine the long-term results of treatment with the Hemopump (Nimbus Medical, Inc., Rancho Cordova, CA) left ventricular assist device. Indications for treatment were postcardiotomy cardiogenic shock (n = 8) and acute cardiac allograft rejection (n = 2). Two of the patients with postcardiotomy shock required a bridge to transplantation. At follow-up (mean, 21 months), eight patients were alive: four were in New York Heart Association Functional Class I and four were in Class II. None had long-term adverse effects that were attributable to the site of insertion (e.g., limb ischemia or infected groin wounds). All the patients considered themselves independent in their daily activities, and most of the patients were able to exercise and pursue hobbies. The Hemopump appears to offer long-term survival with an acceptable quality of life to a population of patients whose survival would have been highly unlikely otherwise.

Activities of Daily Living