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Biomedical subjects

M Phillippe

Publications and source records attributed to M Phillippe.

69 records · Page 4Linked to original sources
PubMed1981

Catecholamines in human amniotic fluid.

This study was undertaken to determine the amniotic fluid levels of epinephrine (E), norepinephrine (N), and dopamine (D) at different gestational ages in the human. Amniotic fluid obtained from 32 pregnant women undergoing amniocentesis for medical indications was analyzed with a radioenzyme assay for these catecholamines. The gestational ages ranged from 17 to 39 weeks. No patient was in active labor at the time of amniocentesis. The data obtained in this study demonstrated a rise of all three catecholamines at the end of the third trimester: N = 362.7 +/- 61.2 pg/ml (+/- SEM), E = 179.6 +/- 45.4 pg/ml (p < 0.05), and D = 2717.0 +/- 836.6 pg/ml (p < 0.01). The physiologic role for the increasing amounts of catecholamines, especially D, in amniotic fluid is known; however, these amines could be the stimulus for the intrauterine synthesis of prostaglandins as parturition approaches.

Amniotic Fluid↗
PubMed1980

Ultrasound-facilitated intrauterine transfusions.

Ultrasound-facilitated intrauterine transfusion was performed on 35 fetuses. Eleven fetuses were hydropic and less than 26 weeks' gestation at the time of the first intrauterine transfusion (IUT). Only two (18%) neonates survived. Twelve fetuses were not hydropic and less than 26 weeks' gestation at time of IUT. Six (50%) neonates survived. Corrected neonatal survival rates for three hydropic and nine nonhydropic fetuses transfused after 26 weeks were 100% and 78%, respectively. The presence of ascites documented by ultrasound is an adequate indication for an IUT and permitted earlier detection of sicker fetuses; however, as a therapeutic aid, ultrasound neither diminished the fetal morbidity and mortality associated with the procedure nor completely eliminated the need for radiography to confirm proper intra-abdominal localization of the transfusion tubing.

Ascites↗
PubMed1980

Pregnancy complicated by the Kasabach-Merritt syndrome.

The Kasabach-Merritt syndrome is the association of cavernous hemangiomas and consumption coagulopathy marked by anemia, thrombocytopenia, and hypofibronigenemia. Exacerbation of the consumption coagulopathy has been described in the 2 previous reports of this syndrome when associated with pregnancy. The authors report a third patient whose delivery and postopartum course were marked by increased coagulation abnormalities and subsequent hemorrhage. This patient's 32-day hospital course and need for multiple blood transfusions, clotting factors, platelets, heparin, and finally epsilon-aminocaproic acid underscore the need for patients with this syndrome to deliver in a referral center hospital where replacement therapy and hematologic consultation are readily available.

Adult↗
PubMedDate not supplied

Steroid hormone modulation of cAMP production in response to beta adrenergic receptor stimulation in genital tract myocytes.

beta-Adrenergic receptor stimulation results in smooth muscle relaxation through activation of adenylyl cyclase and subsequent cyclic AMP (cAMP) production. The present study was performed to evaluate the effects of steroid hormones (i.e. testosterone and hydrocortisone) on beta 2-adrenergic receptors and their signal transduction in the DDT1 MF-2 genital tract myocyte. Radioligand binding studies demonstrated that these two steroid hormones produced a 70 to 80% increase in the density of beta 2-adrenergic receptors in these myocytes. Stimulation of the beta 2-adrenergic receptors with isoproterenol resulted in a significant increase of cAMP in control myocytes; cells treated with testosterone for 24 h demonstrated a comparable response to isoproterenol, whereas hydrocortisone for 24 h resulted in a 50% greater cAMP response. In contrast to the response at 24 h, stimulation of myocytes after testosterone treatment for 48 h resulted in a cAMP response comparable to that seen in response to hydrocortisone at 24 h. Studies performed using theophylline demonstrated similar cAMP responses at 24 h between the control and testosterone-treated myocytes, thereby ruling out the possibility that the delayed increase of the cAMP response after testosterone was caused by stimulation of phosphodiesterase. Direct stimulation with forskolin resulted in greater cAMP production in the testosterone-treated myocytes compared to controls, thereby refuting the possibility that testosterone directly suppresses adenylyl cyclase activity at 24 h. These findings suggest that although both testosterone and hydrocortisone produce a twofold increase in beta 2-adrenergic receptor density in the DDT1 myocytes, beta 2-adrenergic receptors expressed in response to hydrocortisone appear functional at 24 h resulting in increased cAMP production, whereas those expressed in response to testosterone require 48 h to demonstrate increased functional activity.

Animals↗
PubMedDate not supplied

Intracellular signaling and phasic myometrial contractions.

This article reviews recently reported observations regarding the intracellular signal transduction mechanisms involved in the generation of phasic contractions occurring in myometrial tissue. The presence of cell surface receptors for classic uterotonic agonists (including oxytocin, norepinephrine, vasopressin, acetylcholine, and prostaglandins [PGs]) has been well described; all are seven-membrane-spanning, G protein-coupled receptors. Occupancy of these receptors, coupled through members of the Gq and/or Gi families of heterotrimeric G proteins, results in stimulation of the phospholipase C-beta (PLC-beta) isoforms. Nonclassic uterotonic agonists, such as growth factors and cytokines, also activate the phosphatidylinositol (PI)-signaling pathway, in this case through tyrosine kinase receptor-mediated activation of the phospholipase C-gamma (PLC-gamma) isoforms. Several recent reports have demonstrated that activation of the PI-signaling pathway in uterine myocytes results in the development of cytosolic calcium oscillation-like phenomena. These cytosolic calcium oscillations appear to arise from repetitive cycles of emptying and refill of the endoplasmic reticulum calcium stores along with the influx of extracellular calcium. Calcium release from the endoplasmic reticulum calcium stores appears to be mediated by the inositol trisphosphate-sensitive and the ryanodine-sensitive receptor/channels; isoforms for both the these receptor/channels have been shown to be expressed in myometrial tissue. In summary, receptor-mediated activation of the PI-signaling pathway and the generation of cytosolic calcium oscillations appear to produce intermittent calcium transients that result in the development and maintenance of phasic myometrial contractions.

Animals↗
PubMedDate not supplied

Tyrosine kinase-mediated activation of cytosolic calcium oscillations and phasic myometrial contractions.

These studies sought to test the hypothesis that tyrosine kinase-stimulated phasic myometrial contractions are mediated by activation of the phosphatidylinositol (PI)-signaling pathway and the generation of cytosolic calcium oscillations. For these studies, uterine tissue was obtained from adult female Sprague-Dawley white rats during the proestrus/estrus phase of the cycle. In vitro contraction studies were performed using pervanadate (a tyrosine phosphatase inhibitor) with and without inhibitors of the PI-signaling pathway, including 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate (a phospholipase C inhibitor), thimerosal (an inositol-trisphosphate receptor/channel inhibitor), and Ruthenium red (a ryanodine receptor inhibitor), and with oxytocin or prostaglandin F2 alpha (two classic uterotonic agonists). Cytosolic calcium studies were performed using Fura-2-loaded myometrial strips. During these studies, pervanadate was observed to produce cytosolic calcium oscillations and phasic contractions in myometrial tissue comparable to those produced in response to oxytocin and prostaglandin F2 alpha. The pervanadate-stimulated phasic contractions were significantly suppressed in response to inhibition of phospholipase C, the inositol-trisphosphate receptor, and the ryanodine receptor, thereby confirming the importance of the PI-signaling pathway during tyrosine kinase-associated myometrial activity. Further confirming the important and shared role for the PI-signaling pathway during pervanadate-stimulated myometrial contractions, no significant additive effects were observed when classic uterotonic agonists such as oxytocin or prostaglandin F2 alpha were combined with pervanadate.

Animals↗
PubMedDate not supplied

Tissue-specific protein kinase C isoform expression in rat uterine tissue.

OBJECTIVE: Activation of the phosphatidylinositol signaling pathway plays a key role during the generation of agonist-stimulated phasic myometrial contractions. Protein kinase C (PKC), a component of this signaling pathway, has been previously shown to produce feedback inhibition of agonist-stimulated myometrial contractions. The studies described in this report were performed to survey the tissue-specific expression of several PKC isoforms in the rat uterus. METHODS: Uterine tissue was obtained from timed pregnant and normally cycling adult female Sprague-Dawley rats. Immunohistochemical studies were performed using the Vectastain ABC immunostaining technique and PKC isoform-specific polyclonal antibodies. Western blot studies were performed using myometrial tissue separated into cytosol and membrane fractions by differential centrifugation. RESULTS: These studies confirmed significant expression of the PKC-alpha, -beta 2, -delta, -eta, and -zeta isoforms in myometrium from pregnant and estrus rats, whereas only trace or no expression of the PKC-beta 1, -gamma, -epsilon, and -theta isoforms was observed. Expression of the PKC-alpha, -beta 2, and -eta isoforms decreased modestly during the latter days of gestation; in contrast, PKC-delta and -zeta remained stable during this period. The immunohistochemical studies confirmed expression of the PKC-alpha, -beta 2, -delta, -eta, and -zeta isoforms in both circular and longitudinal smooth-muscle layers of the near-term pregnant rat uterus. CONCLUSION: In summary, these studies have confirmed significant levels of expression of several isoforms of PKC in estrus and near-term pregnant rat uterine tissue, which was most prominent in the smooth-muscle cells of the myometrium.

Animals↗
PubMedDate not supplied

The relationship between oxytocin, phosphoinositide-specific phospholipase C, and phasic myometrial contractions.

OBJECTIVES: Oxytocin-stimulated uterine contractions are associated with repetitive cycles of elevated cytosolic calcium, i.e., cytosolic calcium oscillations. The studies in this report were performed to test the hypothesis that phosphoinositide-specific phospholipase C (PI-PLC) is an important component of the myometrial intracellular oscillator. METHODS: In vitro isometric contraction studies were performed using longitudinal strips of myometrium from nonpregnant, adult Sprague-Dawley rats. Cumulative dose-response studies were performed using oxytocin and aluminum fluoride with and without 2-nitro-4-carboxyphenyl-N, N-diphenylcarbamate (NCDC), an inhibitor of PI-PLC. RESULTS: Stimulation of G-proteins coupled to PI-PLC with aluminum fluoride resulted in a significant increase in phasic myometrial contractions comparable to those produced by oxytocin. Inhibition of PI-PLC with NCDC resulted in significant suppression of oxytocin- and aluminum fluoride-stimulated myometrial contractions. In contrast, doses that suppressed agonist-stimulated contractions had only a minimal effect on KCl-stimulated tonic myometrial contractions. CONCLUSIONS: These studies provide significant support for the novel hypothesis that PI-PLC is an important component of the agonist-stimulated cytosolic calcium oscillator that generates phasic myometrial contractions.

Aluminum Compounds↗
PubMedDate not supplied

Constitutive androstane receptor expression in the rat cervix during gestation.

OBJECTIVE: To investigate expression of the constitutive androstane receptor (CAR) in the pregnant rat cervix. METHODS: Rat uterine tissue was obtained on gestational days 12, 16, 20, 21, and 22 (the day of parturition), and postpartum day 1. In addition, liver, lung, kidney, heart, and skeletal muscle tissue were obtained. Expression of the two known CAR isoforms was evaluated using reverse transcriptase-polymerase chain reaction. RESULTS: These studies confirmed CAR expression in the liver; however, CAR was not demonstrated in the myometrium or cervical tissue. CONCLUSIONS: The currently described CAR1 and CAR2 isoforms are not expressed in rat uterine tissue; therefore, they do not appear to participate in parturition in the pregnant rat.

Animals↗
PubMedDate not supplied

The mechanisms underlying Bay K 8644-stimulated phasic myometrial contractions.

OBJECTIVE: Phasic myometrial contractions appear to be produced by calcium transients resulting from the activation of the phosphatidylinositol-signaling pathway. Bay K 8644, an L-type calcium channel activator, produces an increase in frequency and intensity of phasic myometrial contractions. These studies were performed to test the hypothesis that Bay K 8644-stimulated contractions were mediated through mechanisms involving phosphoinositide-specific phospholipase C activation and cytosolic calcium oscillation-like mechanisms. METHODS: In vitro contraction studies and intracellular calcium imaging were performed on longitudinal strips of uterine tissue obtained from mature virgin Sprague-Dawley rats. Isometric contraction data were computer digitized, analyzed for contraction area, and normalized for cross-sectional area. Dose-response studies were performed using previously reported inhibitors of cytosolic calcium oscillation mechanisms. In addition, qualitative inositol-phosphate production studies were performed after prelabeling uterine tissue in vitro with 3H-inositol. Subsequently, the labeled inositol phosphates were separated and recovered using anion exchange chromatography. RESULTS: Bay K 8644 produced periodic calcium transients or oscillations along with a dose-related increase in contractile activity and a significant increase in inositol-phosphate production. In contrast, neomycin (an inhibitor of phospholipase C), adenine (an inhibitor of calcium-induced calcium release), nifedipine (an L-type calcium channel blocker), and EGTA (a calcium chelator) significantly inhibited Bay K 8644-stimulated contractile activity. CONCLUSIONS: These results are consistent with the hypothesis that Bay K 8644, through its facilitation of increased intracellular calcium, results in the activation of the phosphatidylinsitol-signaling pathway and cytosolic calcium oscillation-like phenomena, thereby resulting in the generation of phasic myometrial contractions.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMedDate not supplied

Effects of sodium and calcium channel blockade on cytosolic calcium oscillations and phasic contractions of myometrial tissue.

OBJECTIVE: These studies sought to test the hypothesis that agonist-stimulated cytosolic calcium oscillations and phasic myometrial contractions are dependent on calcium influx through dihydropyridine-sensitive calcium channels, but not sodium influx through tetrodotoxin-sensitive sodium channels. METHODS: Cytosolic calcium imaging studies and in vitro isometric contraction studies were performed using uterine tissue from proestrus/estrus Sprague-Dawley rats. The calcium imaging studies were performed after loading partial thickness strips of myometrium with Fura-2. For the in vitro isometric contraction studies, the contraction data were computer digitalized, analyzed for contraction area, and normalized for cross-section area. The effects of nifedipine (1.0-5 mumol/L), a calcium channel blocker, were compared to tetrodotoxin (0.01-1 mumol/L), a sodium channel blocker. RESULTS: Oxytocin-stimulated simultaneous cytosolic calcium oscillations and phasic contractions were completely inhibited by 1 mumol/L nifedipine; in contrast, 1 mumol/L tetrodotoxin had no effect on the oxytocin-stimulated calcium oscillations and contractions. Oxytocin, aluminum fluoride, potassium chloride, and ionomycin stimulated in vitro phasic myometrial contractions. Tetrodotoxin had no effect on these agonist-stimulated phasic contractions, whereas nifedipine produced a significant, dose-related inhibition of the phasic contractile activity. CONCLUSIONS: The studies described in this report support the hypothesis that the influx of extracellular calcium is an important component of the cellular mechanisms responsible for the cytosolic calcium oscillations occurring during phasic myometrial contractions. In contrast, sodium influx through tetrodotoxin-sensitive sodium channels does not appear to play a comparably important role.

Animals↗
PubMedDate not supplied

Gq-protein alpha subunit expression and distribution in pregnant rat myometrial tissues.

OBJECTIVE: Multiple G-protein isoforms play an integral role in signal transduction; the Gq subtype of G-protein alpha subunits is involved in the activation of the phosphatidylinositol signaling pathway. The studies described herein evaluate the expression of Gq, along with Gs and Gi, in pregnant and nonpregnant rat myometrial tissues. METHODS: Myometrium and other tissues were obtained from nonpregnant and timed-pregnant Sprague-Dawley rats. Western blot studies were performed using polyclonal G-protein isoform-specific antibodies. Immunohistochemical studies were performed using the same antibodies with specimens of myometrium, intestine, and skeletal muscle. RESULTS: The Western blot studies confirmed differential expression of all types of G-protein alpha subunit subtypes in rat myometrial tissues. In pregnant rat myometrium, the expression of Gq and Gs was sustained through day 22, whereas, Gi expression decreased on day 20 and remained low through the remainder of gestation. The immunohistochemical studies revealed significant staining for Gq and Gs in the myometrial layers of the pregnant and nonpregnant rat uterus; in contrast, immunostaining for Gi was minimal in nonpregnant myometrium, and even lower in myometrium from pregnant uteri. CONCLUSIONS: These studies have confirmed expression of the Gq, Gi, and Gs alpha subunits in rat myometrial tissue. Immunohistochemistry confirmed that Gq was expressed at high levels in the myometrial layer of the pregnant and nonpregnant uterus. These observations support the hypothesis that Gq expression is critically important for the transduction of hormone signals, such as those responsible for the generation of phasic myometrial contractions.

Animals↗