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Biomedical subjects

L Baud

Publications and source records attributed to L Baud.

At least 73 records · Page 4Linked to original sources
PubMed1988

Tumor necrosis factor stimulates prostaglandin production and cyclic AMP levels in rat cultured mesangial cells.

Human recombinant tumor necrosis factor-alpha (TNF) was found to stimulate the production of prostaglandins (PG) by cultured rat mesangial cells. This effect was demonstrable from 6 h, was dose dependent and affected the synthesis of PGE2, PGF2 alpha, and 6-keto-PGF1 alpha. It required both RNA and protein synthesis but was not associated with a modification of cell proliferation. TNF also stimulated adenosine 3'-5' cyclic monophosphate (cAMP) levels in the mesangial cell culture medium. Indomethacin suppressed the effect of TNF on PGs but only reduced that on cAMP, indicating that PG production partly mediates the increase in cAMP. These findings demonstrate that mesangial cells can be a target for TNF and that the mechanism of TNF action includes stimulation of both PG production and cAMP levels.

6-Ketoprostaglandin F1 alpha↗
PubMed1988

Leukotriene D4-induced increases in the cytoplasmic pH of human myelocytic leukocytes.

The effects of leukotriene D4 on the intracellular pH of human myelocytes, derived from cultured HL-60 cells by dimethylsulfoxide-induced differentiation, were quantified with the fluorescent indicator 2',7'-bis-(2-carboxy-ethyl)-5,6-carboxyfluorescein. Leukotriene D4, but not C4 or E4, increased intracellular pH optimally by 3 min with a half-maximal effect at 1-2 nM. The increases in intracellular pH stimulated by leukotriene D4 were prevented by pretreatment of myelocytes with leukotriene D4 but not peptide chemotactic factors. Analogs of amiloride that inhibit selectively the Na+/H+ antiport also prevented the intracellular alkalinization induced by leukotriene D4. The rate of recovery of intracellular pH after an acid load with 30 mM sodium propionate was approximately 30% higher at each level of intracellular pH for myelocytes exposed to leukotriene D4 than for those challenged in buffer alone. The increase elicited by leukotriene D4 in the adherence of myelocytic leukocytes to surfaces thus is associated with an enhanced sensitivity of the Na+/H+ antiport to intracellular pH, that is, not coupled to an earlier rise in the cytosolic level of Ca+2.

Calcium↗
PubMed1988

Generation and recognition of leukotriene mediators of hypersensitivity and inflammation.

The potent mediators generated by the 5- and 15-lipoxygenation of arachidonic acid have diverse effects on smooth muscles, blood vessels, leukocytes, epithelial cells and glands, and sensory neurons, which suggest possible roles in the initiation and regulation of physiological and biochemical events. The responses to leukotrienes and related mediators are attributable to binding by stereospecific cellular receptors and consequent activation of biochemical transductional sequences analogous to those characteristic of other receptor systems. The elevated concentrations of these mediators in lesional fluids and tissues of inflammatory bowel disease and other hypersensitivity and inflammatory states are, in some instances, clearly related to the time course of development of the disease process. Systematic application of specific inhibitors and antagonists that are becoming available will define more clearly the involvement of leukotrienes in health and disease and possibly lead to new therapeutic approaches.

Arachidonate 15-Lipoxygenase↗
PubMed1988

Gallium67 scintigraphy in the diagnosis of glomerulonephritis.

To assess the role of gallium-67 (67Ga) scintigraphy in the diagnosis of glomerular diseases, we performed the following technique in 39 patients with glomerulonephritis (GN) who underwent simultaneous Ga scan and histologic examination. 72 hours after IV injection of Ga citrate (2 mCi), isotopic kidney activity (normally undetectable) was compared to the activity of the liver and quantified as follows: less than (1+), equal to (2+) or greater than (3+) that of the liver. Renal biopsy was performed at the same time to evaluate the type of the GN and to quantify interstitial cellular infiltration. Proteinuria, serum albumin and creatinine were measured. There was a significant correlation between the level of 67Ga kidney activity and the degree of proteinuria and hypoalbuminemia. On the contrary, no correlation was found between isotopic activity and the degree of renal failure or the degree of interstitial cellular infiltration. Increased kidney 67Ga activity did not appear characteristic of a specific histologic type of GN. Increased glomerular permeability may alter renal uptake of Ga; therefore 67Ga scanning does not appear to contribute significantly to the diagnosis and the follow-up of either primary or secondary GN.

Biopsy↗
PubMed1988

Radiation-induced lung injuries: a survey by computed tomography and pulmonary function tests in 18 cases of Hodgkin's disease.

Eighteen patients with Hodgkin's disease received chemotherapy and 40 Gy mantle-field irradiation. Radiation-induced lung injuries were studied 5 times during one year for each patient by chest x-ray, CT examination of the thorax and pulmonary function tests. Homogeneous and inhomogeneous densities developed within the radiations ports. They were more often and more easily detected by CT than by chest x-ray (39% vs 11% at the end of the irradiation). CT changes suggested that homogeneous lung density increase and lung nodules corresponded to the radiation pneumonitis phase, also that linear aspects and/or lung condensation aspects corresponded to irradiation-induced lung fibrosis. The displacement of the vessels and the fissures were seen more precisely by CT than by chest x-ray. There was a highly significant correlation between the number of modified areas and the increase in the coefficient of retraction (p less than 0.001).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Modulation of fibroblast proliferation by sulfidopeptide leukotrienes: effect of indomethacin.

Because infiltration of mononuclear cells and fibroblast proliferation are associated in chronic inflammatory lesions, we tested the hypothesis that leukotrienes (LT), a product of activated mononuclear cells, may modulate fibroblast growth. Proliferation of cultured human skin fibroblasts was estimated by [3H]thymidine incorporation and cell count at increasing concentrations (0.1 nM to 0.1 microM) of LTC4 or LTD4. LTC4 and LTD4 stimulated cell growth in a dose-dependent manner only in the presence of 50 microM indomethacin. Under similar conditions, LTE4 but not LTB4 (0.1 microM) was active. Both asynchronous, growing cells and synchronous, quiescent cells were sensitive to LT when prostaglandin (PG) synthesis was suppressed by indomethacin. Other blockers of cyclooxygenase such as ibuprofen and aspirin exhibited identical permissive activity, and the effect of indomethacin was totally abolished by addition of PGE2. LTC4 modified neither [3H]arachidonic acid release from prelabeled fibroblasts nor PGE2 production by fibroblasts. These results demonstrate that the sulfidopeptide LT stimulate fibroblast proliferation only when the endogenous synthesis of PG is blocked, but they do not enhance the synthesis of PG in their target cells showing no evidence for a negative feed-back loop. Nevertheless, it seems likely that the initiation and development of the fibrotic process in the different tissues depends in part on the local balance between PG and LT productions.

Adult↗
PubMed1987

Stimulation by leukotriene D4 of increases in the cytosolic concentration of calcium in dimethylsulfoxide-differentiated HL-60 cells.

The C6-sulfidopeptide leukotrienes C4 (LTC4) and D4 (LTD4) evoked increases in the cytosolic concentration of intracellular calcium ([Ca+2]i) in dimethylsulfoxide-differentiated HL-60 cells, as assessed by the fluorescence of quin-2. The increases in [Ca+2]i reached a peak within 15-90 s, attained 50% of the maximum level at 1.2 nM LTD4 and 60 nM LTC4, were greater in maximal magnitude for LTD4 than LTC4, and subsided in 5-7 min. Flow cytometric evaluation of the LTD4-induced increases in [Ca+2]i, reflected in increases in the fluorescence of intracellular indo-1, revealed that a mean of 77% of differentiated HL-60 cells responded, as contrasted with lesser increases in only 50% of undifferentiated HL-60 cells. The capacity of pretreatment of HL-60 cells with LTD4 to prevent subsequent responses of [Ca+2]i to LTC4 and LTD4, and the finding that the serine-borate inhibitor of conversion of LTC4 to LTD4 suppressed concurrently both LTC4-induced rises in [Ca+2]i and increases in adherence to Sephadex G-25 indicated that the responses of HL-60 cells to LTC4 required conversion to LTD4. That pertussis toxin and a chemical antagonist of LTD4 reduced the [Ca+2]i response suggested a dependence on LTD4 receptors. The LTD4-induced increases in [Ca+2]i were dependent on extracellular calcium and diminished by lanthanum, but not affected by nifedipine nor associated with changes in membrane potential, as measured with the fluorescent probe 3,3'-dipentyloxacarbocyanine. Thus, the increase in [Ca+2]i in HL-60 cells, which is coupled to an increase in adherence, appears to involve LTD4 receptor-specific and voltage-independent calcium channels in the plasma membrane.

Aminoquinolines↗
PubMed1987

Specificity and cellular distribution of human polymorphonuclear leucocyte receptors for leukotriene C4.

Human polymorphonuclear (PMN) leucocytes bind synthetic [3H]-labelled leukotriene C4 ([3H]LTC4) with rapid saturation and reversibility of approximately 90%, by a 700-fold higher concentration of non-radioactive LTC4. [3H]LTC4 is recognized specifically by 10,778 +/- 6260 (mean +/- SD) sites per PMN leucocyte that exhibit a KD of 34.3 +/- 1.7 nM. The specificity of the LTC4 receptors is supported by the competitive inhibition of binding of [3H]LTC4 by LTC4, LTC4-sulphone, LTD4, and LTE4 with relative potencies of approximately 100:20:3:1. The four-fold higher level of specific binding of [3H]LTC4 by sonicates than by intact PMN leucocytes is attributable to intracellular receptors. Of the total number of receptors recovered in sonicates of PMN leucocytes, one-third are associated with membranes and the other two-thirds with lysosomal granules. The affinity of the membrane receptors for LTC4 is indistinguishable from that of receptors on intact PMN leucocytes, whereas the affinity of granule receptors is significantly higher. The characteristics of the receptors are consistent with a role in mediating uptake and metabolism of LTC4 by PMN leucocytes.

Binding Sites↗
PubMed1986

[Early post-radiation pericardial changes in Hodgkin's disease. Value of x-ray computed tomography].

Eighteen patients with mediastinal Hodgkin's disease treated with chemotherapy first, then irradiation were investigated during 1 year by means of 5 CT and radiological examinations of the chest. Four months after irradiation pericardial thickening was detected in 60 p. cent of the patients. The authors underline the high frequency, early occurrence and usually spontaneous resolution of radiation-related pericarditis without clinical or radiological signs.

Adolescent↗
PubMed1986

Leukotrienes and other lipoxygenase products of arachidonic acid synthesized in the kidney.

Lipoxygenase products are synthesized in the kidney. Rabbit medulla and murine and human glomeruli produce 12- and 15-hydroxy-5,8,10,14-eicosatetraenoic acid (HETE). Minor amounts of leukotrienes are formed under normal conditions, but it is likely that the resident renal cells are capable of synthesizing these metabolites. Rat glomeruli and papillae possess the enzymes necessary to process leukotriene C4 into leukotrienes D4 and E4. However, the enzyme activity of the papillae is masked due to the presence of an inhibitor detected in the 10,000 g supernate of the papillary homogenate. 12-HETE synthesis is markedly increased in glomeruli from rats with nephrotoxic serum nephritis and leukotriene B4 synthesis in glomeruli from rats with cationic bovine gamma-globulin-induced glomerulonephritis. In vivo consequences of the association between the resident glomerular cells and the bone marrow-derived cells have been studied in vitro in co-incubation experiments. Glomeruli release factors that stimulate the cyclo-oxygenase and lipoxygenase pathways in macrophages. Co-incubation of glomeruli, platelets, and polymorphonuclear leukocytes results in the formation of 12,20-diHETE and an excess of 12-HETE. Lipoxygenase products, regardless of their origin, modify the renal functions. Leukotriene C4 binds specifically to rat glomeruli and human cultured glomerular epithelial cells. Leukotrienes C4 or D4 administered in vivo cause renal vasoconstriction and a decline in the glomerular filtration rate. In vitro, these two sulfidopeptide leukotrienes promote epithelial cell proliferation and produce mesangial cell contraction. The lipoxygenase pathway is also implicated in the attachment of macrophages to glomeruli and in the oxidative burst of glomerular mesangial cells during phagocytosis. The future use of specific inhibitors of the synthesis or antagonists of the lipoxygenase products, particularly the leukotrienes, should provide a tool for evaluating the role of these metabolites in renal diseases.

Animals↗
PubMed1986

Dexamethasone and hydrogen peroxide production by mesangial cells during phagocytosis.

We have previously demonstrated that a high percentage of rat cultured mesangial cells phagocytized serum-treated zymosan (STZ) (L. Baud, J. Hagege, J. Sraer, E. Rondeau, J. Perez, and R. Ardaillou, J. Exp. Med. 158: 1836-1852, 1983). Phagocytosis resulted in stimulation of arachidonic acid metabolism with generation of H2O2. Exposure of mesangial cells to dexamethasone for 48 h produced a dose-dependent decrease in phagocytosis-induced production of H2O2 with a 50% inhibitory concentration of 32 nM. The decrease in H2O2 release was associated with the inhibition of prostaglandin (PG) E2 production. The effect of dexamethasone could be considered as due to receptor-mediated modulation of protein synthesis since dexamethasone was not active immediately but only after a lag period of 3 h; RU 38486, a potent competitor for dexamethasone receptors, counteracted the reduction in H2O2 generation; and actinomycin and cycloheximide both blunted the inhibitory effect of dexamethasone. Pretreatment of mesangial cells with dexamethasone also produced a dose-dependent decrease in the phagocytic capability of the cells (63% inhibition for 1 microM dexamethasone). However, the inhibitory effect of dexamethasone on H2O2 production expressed as percentage of control was similar whether or not phagocytosis had been blocked by cytochalasin B. This result and also the fact that dexamethasone inhibited H2O2 production in cells triggered with soluble stimuli (A 23187 ionophore, PAF) suggested that the effect of dexamethasone on H2O2 generation was independent of that on phagocytosis. Addition of exogenous arachidonic acid reduced the effect of dexamethasone only when its conversion into PGE2 was inhibited by indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Reactive oxygen species: production and role in the kidney.

Reactive oxygen species (ROS) are formed by incomplete reduction of molecular oxygen. They include superoxide anion (O2-.), hydrogen peroxide (H2O2), hydroxyl radical (OH.), and singlet oxygen (1O2). ROS may induce different types of cell injury, particularly lipid peroxidation and membrane damage. ROS have been shown to play an essential role in the mechanisms of experimental models of several renal diseases: ischemic acute renal failure, renal graft rejection, acute glomerulonephritis, and toxic renal diseases. They are produced by the renal cells and also by the inflammatory bone marrow-derived cells invading the renal tissue. ROS, regardless of their origin, may degrade the glomerular basement membrane and alter the glomerular and tubular cell functions. Particularly, they produce an increase in cyclic AMP synthesis and prostaglandin production in the glomeruli. Recent studies have shown that the glomerular mesangial cells themselves generated ROS on stimulation by phagocytosis of foreign particles or exposure to the complement membrane attack complex or platelet-activating factor. Production of ROS is in narrow relationship with the metabolism of arachidonic acid. Conversion of this fatty acid via the lipoxygenase pathway is associated with an increase of ROS, whereas its transformation into prostaglandins via the cyclooxygenase pathway results in the opposite effect. Production of ROS in activated mesangial cells can be inhibited by glucocorticoids via a receptor-mediated mechanism. The fact that some of these characteristics are different in leukocytes suggests the possibility in the future of the more specific pharmacological control of the inflammatory process in the glomerular mesangium.

Acute Disease↗