Biomedical subjects
Publications and source records attributed to W Bertrand.
The authors present their experiences in assisting the government of Niger to develop automated information systems for health care management. They discuss the structure of the health system, the role of donor assistance, the process of initiating automated systems, and the technical requirements and costs of the system. Finally, they draw general conclusions that may be useful for those attempting similar efforts.
This study examines the relationship between severe diarrhoeal disease and maternal knowledge and behaviours related to hygiene and sanitation. Some 107 paediatric cases admitted to two hospitals in Kinshasa, Zaire in 1988 were matched on age and nearest-neighbour status to 107 controls. Personal interviews and observational methods were used to assess knowledge and behaviours related to hygiene and sanitation. Cases and controls had equivalent socioeconomic status, demographic profiles and access to water and sanitation facilities. However, cases generally exhibited lower levels of knowledge and less sanguine sanitary practices than did controls. Of particular interest was the finding that very specific behavioural items distinguished cases from controls. The disposal of the child faeces and household garbage and mother's knowledge that poor caretaker cleanliness was a cause of diarrhoea in children showed the strongest associations with risk of diarrhoea. There was an exponential relationship between the number of these items a mother answered incorrectly and the odds of diarrhoeal disease. The risk attributable to these three variables was as high as 70%. These findings provide further support for the view that focused educational interventions may have a substantial impact on the occurrence of severe diarrhoeal disease in low-income countries.
The cytokines, interleukin-1 (IL-1) and tumor necrosis factor (TNF), potently induce prostaglandin formation in glomerular mesangial cells. Mechanisms by which these cytokines stimulate prostaglandin formation vary among cell types. We investigated whether alterations in phospholipase A2 (PLA2) or cyclooxygenase (COX) mass and activity contribute to the changes in mesangial cell prostaglandin production. These cytokines induced COX activity and mass in a time-dependent manner, which paralleled prostaglandin production. IL-1 increased COX mass approximately threefold by 24 h. TNF had a much smaller effect, although it appeared to be additive with IL-1. IL-1-induced COX mass was maintained at an increased level for at least 48 h. The glucocorticoid dexamethasone (DEX) virtually abolished prostaglandin production and blocked cytokine induction of COX activity and mass. DEX did not reduce COX activity or mass below the basal, serum-fed levels, however. By utilizing stable isotope methods, we could demonstrate that IL-1 increased free arachidonate levels, implying new PLA2 synthesis over a time course that was maximal at 6 h and was cycloheximide and actinomycin D sensitive. These data demonstrate that the cytokines IL-1 and TNF enhance synthesis of COX and PLA2, contributing to increased prostaglandin production. Cytokine-stimulated prostaglandin production ceases when cells are also treated with DEX, although control levels of COX activity and mass remain. This occurs because DEX inhibits the IL-1-induced enhanced arachidonate release.
To evaluate the identity of the guanosine triphosphate--binding proteins coupling arginine vasopressin receptor occupancy with activation of phospholipase C, leading to Ca2+ mobilization, and activation of phospholipase A2, leading to arachidonate release and prostanoid formation, we used intact cells, saponin-permeabilized cells, and membranes of the rat mesangial cell. Arginine vasopressin 10(-7) mol/L produced a dose-dependent increase in cytosolic Ca2+ to maximal levels of 500 nmol/L with peak responses occurring within 10 seconds of addition of arginine vasopressin to cells in suspension. Arginine vasopressin 10(-7) mol/L elicited a maximal response. These increases were associated temporarily with a fourfold increase in tritiated D-myo-inositol 1,4,5-trisphosphate formation in prelabeled cells. Pertussis toxin (200 ng/ml) did not inhibit the Ca2+ increase nor did it inhibit the increase in tritiated D-myo-inositol 1,4,5-trisphosphate formation, suggesting a pertussis toxin--insensitive signaling pathway for phospholipase C hydrolysis in response to vasopressin. Membranes prepared from mesangial cells increased D-myo-inositol 1,4,5-trisphosphate formation in vitro in response to arginine vasopressin and guanosine-5'-0(3- thiotrisphosphate), and this stimulation was inhibited by guanosine-5'-0(2-thiodiphosphate), confirming the involvement of a guanosine triphosphate--binding protein. In contrast arginine vasopressin stimulated arachidonate release from intact mesangial cells, and this effect was blocked by pretreating cells with pertussis toxin. To demonstrate that this was through a pertussis toxin--sensitive guanosine triphosphate--binding protein, we permeabilized cells with saponin and determined that arginine vasopressin and guanosine-5'-0(3-thiotriphosphate) stimulated the release of arachidonic acid and the stimulation of guanosine-5'-0(3-thiotriphosphate) was inhibited by guanosine-5'-0(2-thiodiphosphate). Finally, pertussis toxin was able to stimulate adenosine diphosphate ribosylation in vivo of a substrate protein in mesangial cell membranes of 41 kd, and this ribosylation was inhibited by pretreating cells with pertussis toxin. These data suggest that the release of arachidonic acid by vasopressin in glomerular mesangial cells is linked to a pertussis toxin--sensitive guanosine triphosphate--binding protein and that this activation of phospholipase C in vasopressin is linked to a pertussis toxin--insensitive guanosine triphosphate--binding protein.
Earlier studies on LLC-PK1 cells have demonstrated two pharmacologically distinct Na+/H+ exchangers in renal epithelia. In addition, the cDNA clone for the human Na+/H+ antiporter which is growth factor activatable has been isolated and expressed (Sardet, C., Franchi, A., and Pouyssegur, J. (1989) Cell 56, 271-280). We report here the synthesis of an amiloride analogue that can be photoactivated and labeled with 125I. This analogue covalently cross-links a 66-kDa protein of bovine renal brush border membranes. A rabbit polyclonal antibody that was directed against a 20-amino acid peptide of the cytoplasmic domain of its human Na+/H+ antiporter also gives a positive Western against 66-kDa protein of bovine brush border membranes. Thus, the photoactive probe may be helpful in the isolation and purification of the brush border Na+/H+ exchanger.
In order to assess whether changes in intracellular Ca2+ are necessary for bradykinin stimulated activation of phospholipase A2 and PGE2 production, MDCK cells were treated with phorbol myristate acetate (PMA) and Lanthanum (La3+). 100 nM PMA reduced peak BK (1 uM) stimulated Ca2+ to 44.0 +/- 11.4% of control, while 1 mM LaC13 reduced peak Ca2+ to 43.5 +/- 12.2% of control. Addition of both PMA and LaC13 reduced the BK stimulated change in intracellular Ca2+ to 8.3 +/- 1.0% of control. In contrast, La3+ did not reduce PGE2 production in response to 10(-7) M to 10(-5) M BK. PMA stimulated PGE2 production, as shown previously. Addition of both PMA and La3+ at doses capable of reducing Ca2+ changes to less than 10% of normal, failed to block BK induced PGE2 production. Therefore, BK stimulated PLA2 activation and PGE2 production can be dissociated from changes in intracellular Ca2+ and suggest that BK activates PLA2 through a mechanism other than by increases in intracellular Ca2+.
The tumor promoter phorbol ester (PMA) has been shown to stimulate protein kinase C (PKC) in MDCK cells. At the concentrations that produce stimulation of PKC, PMA (100 microM) inhibits BK-induced I1,4,5P3 (IP3) formation and calcium transients in these cells. 1-5-isoquinolinyl-2-methyl-piperazine (H7) a known inhibitor of PKC in MDCK cells reverses the effect of PMA on BK-stimulated IP3 formation and Ca2+ transients in these cells. PMA also stimulates arachidonate release which can be inhibited by preincubation with H7. A dual mechanism of regulation by PKC at the level of phospholipase C (down regulation) and phospholipase A2 (stimulation) is suggested in these cells.
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To describe the causes of growth failure in a developing country, we studied family food availability, anthropometric measurements of preschool children, and family and neighborhood socioeconomic conditions in a stratified random sample of Cali, Colombia families. The influences on preschool child growth of food availability, neighborhood socioeconomic conditions, and family socioeconomic conditions were separated statistically. Neither food availability nor other family factors were related directly to growth, but neighborhood factors did have a strong relationship to growth. Children decreased progressively from 97.5 percent of expected weight in the top one-sixth of neighborhoods we studied to 89 per cent in the botton one-sixth. Food availability, although not related to growth, was strongly related to family factors. The top one-sixth of families had 115 percent of FAO (Food and Agricultural Organization) protein allowances, while the bottom one-sixth had only 75 per cent. These finding are inconsistent with food availability or family factors being the prinicipal causes of growth retardation. They are consistent with neighborhood determined factors, possibly enteric infections, being the principal cause of growth retardation in preschool children in Cali.
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