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Biomedical subjects

J Perez

Publications and source records attributed to J Perez.

At least 199 records · Page 11Linked to original sources
PubMed1988

Sexual differentiation of the neuronal plasma membrane: neonatal levels of sex steroids modulate the number of exo-endocytotic images in the developing rat arcuate neurons.

Exo-endocytotic images and intramembrane protein particles (IMP) were quantitatively assessed in freeze-fracture replicas from the plasma membrane of arcuate neurons of rats aged 0 (newborns), 10, 20 and 100 days postpartum. Membranes contained significantly (P less than 0.02) more IMPs in females than in males. Exo-endocytotic images were increased in newborn and 10-day-old males when compared to adult males or to developing females (48 +/- 6 vs 6 +/- 1 images/100 micron 2 in 10-day-old male and female rats, respectively). Androgenization of females with a single injection of testosterone propionate on the day of birth resulted in an increased number of exo-endocytotic images in developing animals (75 +/- 9 images/100 micron 2, 10-day-old rats) and in the abolishment of the sex differences in the number of IMPs.

Aging↗
PubMed1988

Anisotropy of the ultrasonic backscatter of myocardial tissue: II. Measurements in vivo.

The purpose of this investigation was to determine the angular dependence of the backscatter from canine myocardial tissue in vivo and to compare it with the variation of backscatter over the cardiac cycle that has been recognized and reported previously. The backscatter was measured from regions of left ventricular wall in canine hearts in which the fibers of the muscle lay parallel to the surface of the heart and were oriented predominantly in a circumferential fashion. Because of technical considerations, the angle of insonification was varied systematically through two cycles in which the angle relative to the muscle fiber axes ranged from 60 degrees-120 degrees. Backscatter was maximum at angles of interrogation perpendicular to the myocardial fibers and minimum at those most acute (60 degrees) relative to the orientation of the fibers. The previously observed variation of integrated backscatter over the heart cycle was evident at each angle of interrogation. At end systole, the average maximum-to-minimum angular variation of integrated backscatter as 5.0 +/- 0.4 dB. At end diastole, the average maximum-to-minimum angular variation was 3.2 +/- 0.4 dB. Thus, even though angular dependence of the backscatter from tissues with directionally oriented structures is substantial, the anisotropy does not account for cardiac-cycle-dependent variation of backscatter. Accordingly, the angular dependence should be incorporated in approaches to quantitative tissue characterization with ultrasound.

Animals↗
PubMed1988

Estrogen modulation of the gamma-aminobutyric acid receptor complex in the central nervous system of rat.

Administration of estradiol benzoate to ovariectomized rats results in an increased binding of [3H]muscimol, [3H]diazepam and 35S-t-butylbicyclophosphorothionate in various areas of the central nervous system of rats. The effect is dose-dependent and its onset can be observed as early as 12 hr after s.c. administration of the hormone. The various binding activities are differentially affected by the hormonal treatment: the maximal effect observed for [3H]diazepam binding is in the cerebellum (+42%), for [3H]muscimol binding in the frontal cortex (+84%) and for 35S-t-butylbicyclophosphorothionate binding in the striatum (+46%) indicating that the activities of the sites are not under the same cellular regulatory control. The estrogen-induced increase in [3H]diazepam binding sites does not result in an increased protection against chemoconvulsants such as pentylenetetrazole.

Animals↗
PubMed1987

Relationship between elevated plasma levels of crosslinked fibrin degradation products (XL-FDP) and the clinical presentation of patients with myocardial infarction.

To assess whether the intense thrombotic state known to occur early after the onset of acute myocardial infarction is further exacerbated by impaired intrinsic fibrinolysis, we compared the intensity of fibrinolysis as measured by the level of crosslinked fibrin degradation products (XL-FDP) in plasma with the intensity of thrombosis as assessed by fibrinopeptide A (FPA) in 98 patients with transmural and 14 patients with non-Q wave infarction. Patients without complications of infarction such as shock, mural thrombi, or malignant arrhythmias requiring countershock generally had normal plasma levels of XL-FDP, less than or equal to 300 ng/ml (81% of those presenting less than 8 hours after onset and 66% of those presenting greater than 8 hours after onset) on admission despite elevated FPA indicative of ongoing thrombosis. In contrast, patients with complications generally had elevated levels of XL-FDP greater than 300 ng/ml (80% of those presenting early and 62.5% of those presenting late) and 50% of these patients had marked elevations to greater than 1000 ng/ml. FPA was markedly elevated in patients with complications whether they presented early or late after onset of infarction. Our direct measurements at the time of infarction support previous data indicating that intrinsic fibrinolysis is impaired in patients with acute infarction, despite marked thrombin activity, when complications are not present. However, when complications are present initially, a more exuberant fibrinolytic response is observed perhaps due to thrombosis associated with the complications themselves.

Female↗
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↗
PubMed1986

Estrogen-induced up-regulation of gamma-aminobutyric acid receptors in the CNS of rodents.

Previous studies have identified an effect of estrogen administration on the number of central GABAergic binding sites of rat. We have further characterized this effect by performing a series of experiments in vitro where we analyzed the changes of gamma-aminobutyric acid (GABA) binding in slices of nervous tissue incubated in a physiological medium in presence of estradiol. The tissues were dissected from ovariectomized rats. In such a system, estrogen augmented the amount of [3H]muscimol binding within 3 h of incubation. The effect was dose-dependent and could be blocked by the addition of the anti-estrogen tamoxifen. The increase in [3H]muscimol binding could not be observed by addition of estradiol to broken membranes or by incubation of the slices with steroids deprived of estrogenic activity. Furthermore, the estrogen-induced increase of GABA binding sites could be prevented by addition of cycloheximide and alpha-amanitin in the incubation medium. Our data indicate that the estrogen may increase the number of GABA binding sites by direct interaction with the GABA receptor gene or genes involved in the metabolism of GABA receptor.

Animals↗
PubMed1986

Sexual dimorphism in the response of the GABAergic system to estrogen administration.

Administration of estradiol benzoate to gonadectomized female rats results in up-regulation of CNS gamma-aminobutyric acid (GABA) receptors. The increase of [3H]muscimol binding activity is observed in six of the seven brain areas examined. The same treatment, performed in castrated male or androgenized female rats, induced an increase of [3H]muscimol binding only in the striatum. Evidence is provided suggesting that the dimorphic sensitivity of GABA receptor is not correlated with the difference in spontaneous motor activity reported between male and female rats.

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↗
PubMed1985

Role of female gonadal hormones in the CNS: clinical and experimental aspects.

The large body of evidence presented indicates that in the brain the action of sex hormones cannot be thought as restricted to the regulation of endocrine functions and mating behavior. Estrogens and progesterone seem to act in numerous regions of the CNS to regulate motor as well as limbic functions. Furthermore, the data reviewed indicate that these hormones may modulate neuronal activity through a wide variety of mechanisms. More studies should focus on such mechanisms in order to better understand the role of sex hormones in the CNS and to devise ways of limiting their effects on depression, epilepsy etc. It is known that in peripheral target organs these hormones modulate cell activities by binding to specific receptors which can recognize the DNA sequence and activate the transcription of selected genes (135, 136). There is evidence supporting the hypothesis that this mechanism of action has been conserved also in the brain. First, the brain receptors for progesterone and estrogens are functionally and biochemically indistinguishable from those in the periphery (4, 5): they may be concentrated in neuronal nuclei and bind chromatin "in vitro" (7). Second, a temporal relationship has been observed between administration of steroids and the increase of polymerase II activity (137) and protein synthesis (4, 5). Third, various hormone-induced behaviors may be blocked by inhibitors of the protein synthesis (138, 139, 140, 141). However, sex hormones must be capable to regulate neuronal functions by mechanisms other then genomic. In fact, the topical application of estrogen or progesterone on nervous tissue results in a rapid change of membrane potential (60, 71). Such a rapid effect is not likely to be the consequence of nuclear action, but rather must be related to events occurring on the cell surface. It has been hypothesized that sex steroids affect the fluidity of the cell membrane, therefore modifying the ion transport or neurotransmitter receptor activity (142). If this were the case we would expect to observe a similar effect after application of any steroid. Experimental evidence demonstrates that not all the steroids affect the nervous membrane potential. Moreover, two steroids, estradiol and progesterone, have been described to modulate membrane potential in an opposite way (66, 67, 69, 75). At the moment, there is no evidence for the presence of steroid receptors on neuronal membranes which could mediate the described phenomena.(ABSTRACT TRUNCATED AT 400 WORDS)

Amygdala↗
PubMed1985

Progesterone in rat brain: modulation of beta-adrenergic receptor activity.

Cytosolic proteins binding specifically the progesterone analogue 3H R5020 can be detected in various areas of the central nervous system (CNS) of rat. Our study demonstrates that the concentration of progesterone receptors in the brain of adult, ovariectomized, female rats is maximal in frontal cortex and midbrain and lowest in the cerebellum. Short term administration of the hormone does not alter the beta-adrenergic receptor system, while a prolonged administration of progesterone results in an up-regulation of 3H-DHA binding in the frontal cortex. Such increase in binding activity is due to an increased number of beta-adrenergic receptors. Furthermore, high doses of progesterone can also increase the number of beta-adrenergic binding sites in an "in vitro" system where brain slices are incubated for few hours in a physiological medium.

Animals↗
PubMed1985

Differential stimulation of PGE2 synthesis in mesangial cells by angiotensin and A23187.

The mechanism of arachidonic acid release and prostaglandin E2 (PGE2) synthesis was studied in cultured mesangial cells from rat kidneys. Both the ionophore A23187 and angiotensin II stimulated radioimmunoassayable PGE2 synthesis. The effect of angiotensin occurred within minutes, with half-maximal stimulation around 10(-9) M. In cells prelabeled with [14C]arachidonate, A23187 caused release of [14C]-arachidonate from all phospholipids. In contrast, angiotensin II caused preferential release of [14C]arachidonate from phosphatidylinositol, associated with a significant increase in 14C-labeled phosphatidic acid, mono- and diacylglyceride, and arachidonate. These results indicate that angiotensin preferentially, but not exclusively, stimulates a phosphatidylinositol-specific phospholipase C, whereas A23187 results in unspecific stimulation of phospholipases. The tight coupling between an angiotensin-responsive phospholipid-arachidonate pool and cyclooxygenase may be responsible for the specificity of the response to angiotensin.

Angiotensin II↗
PubMed1985

Fibrinopeptide A: a marker of acute coronary thrombosis.

To determine whether coronary thrombosis in vivo is reflected by elevations in levels of fibrinopeptide A (FPA) in plasma, we sequentially characterized plasma FPA levels associated with evolving infarction in patients admitted to the cardiac care unit early after the onset of symptoms, in patients with transmural infarction admitted later, and in patients with nontransmural infarction. Studies were also performed in patients in whom the diagnosis of infarction was suspected but subsequently excluded. FPA values were significantly higher in patients with transmural infarction (42.3 +/- 11.2 ng/ml [mean +/- SEM], n = 53) compared with those in patients with nontransmural infarction (4.8 +/- 1.6 ng/ml, n = 17) or with those in patients in whom infarction was subsequently excluded as a diagnosis (3.5 +/- 0.6 ng/ml, n = 17, p less than .01 for both). Elevations in FPA level were greatest in patients with transmural infarction from whom samples were obtained soon after the onset of symptoms. Thus, in 39 patients from samples were obtained within 10 hr after the onset of symptoms, FPA levels were significantly higher than in 14 patients from whom samples were obtained initially more than 10 hr after the onset of symptoms (55.5 +/- 14.7 vs 4.9 +/- 1.4 ng/ml, p less than .01). In 30 of the 39 patients with evolving transmural infarction from whom samples were obtained within the first 10 hr after the onset of symptoms, the level of FPA was greater than 8 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease↗
PubMed1985

Variability of airway responsiveness to histamine aerosol in normal subjects. Role of deposition.

The purpose of this investigation was to determine if the variability of bronchial responsiveness to inhaled histamine in normal subjects is related to the total dose of histamine deposited in the airways. To test this possibility, we used a new method of histamine challenge that permits calculating the histamine mass deposited in the airways in an attempt to correlate it with the magnitude of the response. Using a standardized breath-holding maneuver, 10 healthy nonsmokers and 10 healthy smokers with normal spirometry inhaled an aerosol generated from a solution containing a fixed ratio of histamine and a small quantity of hematoporphyrin serving as a fluorescent tracer. The mass of histamine deposited was calculated from the measured fluorescence of the inspired and expired aerosol. Forced expiratory volume in one second (FEV1) was measured before and 10 min after inhalation challenge. There was a negative correlation between percent decrease in FEV1 (delta FEV1) and histamine mass deposited in the nonsmokers (r = -0.83, p less than 0.005) and smokers (r = -0.82, p less than 0.005) without a difference between the 2 slopes. The range of delta FEV1 was 7 to 33% and of histamine mass deposited, 0.02 to 0.18 mg in the nonsmokers. The respective values in the smokers were 2 to 30% and 0.02 to 0.17 mg. In 6 subjects in whom dose-response curves were obtained, the mean deposited histamine mass required to decrease the FEV1 by 10% was 0.11 mg.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Leukotriene C4 binds to human glomerular epithelial cells and promotes their proliferation in vitro.

In human and experimental glomerulonephritis, glomerular hypercellularity results both from accumulation of macrophages and proliferation of resident glomerular cells. The recent identification of macrophage-derived factors that stimulate mesangial and epithelial cell proliferation suggests that these factors might contribute to the hypercellularity. To determine the identity of such macrophage-derived growth factors, we studied the effect of leukotrienes (LTs), products that are released from macrophages and leukocytes, on proliferation of human glomerular epithelial cells in culture. Dose-dependent (1-100 nM) stimulation of [3H]thymidine incorporation, an index of cell proliferation, was observed in cells incubated with the sulfidopeptide LTs, LTC4 and LTD4, but not with LTB4. The response was 248 and 172% of control values at 100 nM LTC4 and LTD4, respectively. This effect of LTC4 was abolished by FPL 55712. Subsequent binding studies demonstrated that glomerular epithelial cells possess specific receptors for LTC4. [3H]LTC4 bound rapidly at 8 degrees C to the cells. There was a plateau after 40 min incubation. Maximum specific binding was 70-90% of total binding. Specific binding was totally reversible with addition of an excess of unlabeled LTC4. Analysis of time-course association slopes at two concentrations of [3H]LTC4 and of the competition between a single concentration of [3H]LTC4 and increasing concentrations of unlabelled LTC4 allowed calculation of dissociation constants (Kd) of 220 and 217 nM, respectively. Both LTD4 and LTE4 exhibited ED50 values that were at least one order of magnitude higher than for LTC4. Thus, our findings suggest that LTC4 binds to specific receptors of glomerular epithelial cells, promotes proliferation of these cells, and could contribute to epithelial hypercellularity found in glomerulonephritis.

Cell Division↗
PubMed1984

Progesterone and estrogens in rat brain: modulation of GABA (gamma-aminobutyric acid) receptor activity.

Our data indicate that estrogens and progesterone can regulate the number of GABA receptors (as detected by [3H]muscimol binding assay) in rat brain. Both hormones act in selected areas. The extent of the effect (up to 160% increase) and the number of areas responsive suggest that sex hormones may play a very important role in the regulation of the functions of GABAergic transmission in the central nervous system.

Animals↗
PubMed1984

Effect of platelet-activating factor and serum-treated zymosan on prostaglandin E2 synthesis, arachidonic acid release, and contraction of cultured rat mesangial cells.

The interaction of inflammatory cells and glomerular prostaglandins (PG) may be important during glomerulonephritis. We therefore examined the influence of platelet-activating factor (PAF), (a mediator of inflammation released from leukocytes) and of phagocytosis of zymosan on arachidonic acid metabolism and on cell contractility in rat glomerular mesangial cells in culture. PAF increased PGE2 synthesis (determined by radioimmunoassay) within minutes (threshold: 10(-10)M; maximal effect: 10(-7)M). Serum-treated zymosan also stimulated PGE2, but with a slower onset. In cells prelabeled with [14C]arachidonic acid both PAF and serum-treated zymosan released 14C from phospholipids and increased free [14C]arachidonate. The ratio of 14C-release to PGE2 was, however, different with PAF and serum-treated zymosan, indicating different phospholipid pools. Under phase-contrast microscopy, PAF caused contraction of mesangial cells with a dose-response and time-course parallel to that for PGE2 synthesis. Serum-treated zymosan caused no contraction. The PAF-induced contraction was enhanced by PG synthesis inhibition and was attenuated by addition of PGE2, indicating a feedback mechanism. The mesangial contraction by PAF may be important in favoring deposition of immune complexes, while the PGE2 synthesis stimulated by PAF and by phagocytosis of zymosan may counteract the deleterious effects of PAF during induction of glomerulonephritis.

Animals↗
PubMed1983

Reactive oxygen production by cultured rat glomerular mesangial cells during phagocytosis is associated with stimulation of lipoxygenase activity.

To investigate the phagocytic capability of glomerular mesangial cells and the biochemical events associated with phagocytosis, rat cultured mesangial cells were incubated in the presence of opsonized zymosan (STZ) and production of reactive-oxygen species and lipoxygenase products were determined. Mesangial cells were identified on the basis of morphologic (presence of microfilaments and pattern of staining by an anti-myosin antiserum) and physiologic (contractile activity in response to angiotensin II) characteristics. No contamination by esterase-positive cells was observed. Electron microscopy revealed that the phagocytic process started after 5 min of incubation, and affected approximately 50% of the cells. Superoxide anion (.O2-) and hydrogen peroxide (H2O2) generation by mesangial cells exposed to STZ increased with time and STZ concentration. Cells incubated with zymosan particles treated with heated serum produced undetectable amounts of .O2- and 6 times less H2O2 than cells exposed to STZ. Pretreatment by cytochalasin B produced a marked decrease in STZ-stimulated production of reactive oxygen species. [3H]Arachidonic acid was incorporated into mesangial cell phospholipids and its release and conversion into monohydroxyeicosatetraenoic acids (HETE) was measured by radiometric high performance liquid chromatography (HPLC). Incubation with STZ markedly stimulated the release of arachidonic acid from its phospholipid stores and its transformation into 11-, 12-, and 15-HETE. Lipoxygenase inhibitors inhibited STZ-stimulated H2O2 production, whereas they did not modify the phagocytic process as shown by the absence of any effect on the uptake of 125I-STZ by the mesangial cells. This study demonstrates that a high percentage of rat cultured mesangial cells phagocytose opsonized particles. The phagocytic process results in an oxidative burst that appears to be dependent on stimulation of the lipoxygenase pathway.

Animals↗