Biomedical subjects

C Roman

Publications and source records attributed to C Roman.

At least 37 records · Page 2Linked to original sources

PubMed1998

Endothelin-receptor blockade does not alter closure of the ductus arteriosus.

Endothelin-1 (ET-1) is synthesized within the wall of the ductus arteriosus (DA) and is a potent constrictor of the DA in vitro. However, the role of endogenous ET-1 in closure of the DA at birth remains unclear. Therefore, we studied the effects of a selective ETA-receptor antagonist (PD-156707), or its vehicle, on DA closure in 13 late-gestation fetal lambs during the first 5 h after birth. We also studied the effects of ETA-receptor blockade on DA constriction induced by oxygen, indomethacin (a cyclooxygenase inhibitor), and LY-83583 (a soluble guanylate cyclase inhibitor) in vitro (n = 9 ductus arteriosus rings). In vehicle-treated lambs in vivo, the DA constricted during the 5-h study period after birth: DA resistance increased (from 0.007 +/- 0.01 to 3.406 +/- 4.15 mmHg. ml-1. min. kg-1; P < 0.05); the pressure gradient across the DA increased (from 1.4 +/- 2.1 to 25.2 +/- 9.4 mmHg; P < 0.05); and DA blood flow decreased (from 193.5 +/- 48.0 to 19.3 +/- 14.3 ml. kg-1. min-1; P < 0.05). In vitro, the DA was constricted by exposure to 30% oxygen (23 +/- 14% net active tension; P < 0.05), indomethacin (5 x 10(-6) M, 22 +/- 5% net active tension; P < 0.05), LY-83583 (10(-5) M, 24 +/- 10% net active tension; P < 0.05), and ET-1 (10(-7) M, 19 +/- 4% net active tension; P < 0.05). Although PD-156707 blocked both the in vivo and in vitro effects of exogenous ET-1, it had no effect on postnatal ductus constriction nor on in vitro ductus contractile responses to oxygen, indomethacin, or LY-83583. This study suggests that endogenous ET-1 does not play an important role in closure of the DA at birth.

Animals↗

PubMed1998

[Deglutition: physiologic and neurophysiologic aspects].

Swallowing is a complex motor sequence involving the coordinated contraction of many muscles of the buccopharyngeal cavity, the larynx and the oesophagus. Most of the muscles are striated except those of the distal oesophagus which, in human and some other species, are of the smooth type. During swallowing, usually divided into a buccopharyngeal and an oesophageal stage (peristalsis), the sequential activity of the muscles results from motor orders programmed by a rhombencephalic swallowing centre and conveyed to the periphery by efferent fibres belonging to various pairs of cranial nerves (Vth, VIIth, Xth, XIIth). Apart from the motor nuclei of the cranial nerves, the swallowing centre contains an interneurone network responsible for the programming of deglutition. During swallowing, these interneurones (INs) exhibit a sequential activity quite parallel to that of muscles, and persisting in the absence of sensory feedback. The "swallowing INs" are located in two medullary regions: (1) a dorsal region including the nucleus of the solitary tract and the adjacent reticular formation, (2) a ventral region corresponding to the reticular formation surrounding the nucleus ambiguus. The dorsal INs are involved in the initiation and the programming of swallowing. The ventral INs receive their swallowing input from the dorsal neurones and are probably switching neurones that distribute the swallowing excitation to the various pools of motoneurones. The swallowing program can be triggered by inputs originating from either the peripheral reflexogenic areas or the supramedullary structures (cerebral cortex, basal ganglia and hypothalamus). Under physiological circumstances swallowing program is continuously modified by peripheral afferents (expecially muscular) that adjust the force and the timming of contractions to the size of the swallowed bolus. In addition, an important operating feature of the programming network consists of a functionnal polarization so that the activity of proximal portions of the swallowing tract inhibits that of distal portions. This polarization implies the existence of inhibitory connections between interneurones, that could be responsible for the series of delays typical fo swallowing contractile sequence, by generating delayed desinhibitions followed by post inhibitory excitations. Lastly, the sensitive messages that trigger and adjust the swallowing program are at the same time conveyed to higher nervous structures allowing the so called "voluntary" swallow and the integration of swallowing in the ingestive behavior. Disruption of this central loop is likely the source of swallowing disorders (dysphagia) following lesion of cortical or subcortical structures.

Animals↗

PubMed1997

Fetal and maternal hemodynamic and metabolic effects of maternal nitroglycerin infusions in sheep.

OBJECTIVES: We previously demonstrated effective tocolysis with nitroglycerin in laboring sheep. In this study we evaluated maternal and fetal circulatory effects of nitroglycerin. STUDY DESIGN: Vascular catheters and an umbilical Doppler flow transducer were placed in eight ewes. Nitroglycerin was infused maternally over 30 minutes at 1.5, 2.5, 5.0, and 10 microg x kg maternal weight(-1) x min(-1). We recorded maternal and fetal variables before, at the end of each 30-minute infusion period, and 30 minutes later. Fetal regional flow distribution was measured with microspheres. Fetal oxygen, glucose, and lactate uptake were calculated. Data were analyzed by analysis of variance. RESULTS: There were no changes in fetal blood gas values, oxygen or substrate uptake, umbilical flow, output distribution, pressures, or heart rate. Maternal mean pressure fell and heart rate increased concomitantly. Maternal blood gases were unchanged. CONCLUSION: Nitroglycerin at tocolytic and greater doses had no adverse effects on fetal circulatory function during a 2-hour infusion.

Animals↗

PubMed1997

Markers of haemostatic activation before and after blood donation and plasmapheresis.

BACKGROUND AND OBJECTIVES: Previous studies have reported signs of haemostatic activation after haemorrhage. The aim of this study was to measure sensitive markers for haemostatic activation after blood donation or plasmapheresis in healthy donors. MATERIALS AND METHODS: Blood samples were drawn before as well as 5 min and 1 h after donation in 40 male donors, of whom 29 gave 1 unit of blood and 11 underwent plasmapheresis. Standard assays were used. RESULTS: Plasma concentrations of the activation markers prothrombin fragment 1 + 2, thrombin-antithrombin complexes, and von Willebrand factor did not increase after blood or plasma donation. CONCLUSIONS: In our opinion, these procedures are safe.

Adult↗

PubMed1997

Intracellular activity of motoneurons of the rostral nucleus ambiguus during swallowing in sheep.

The nervous mechanisms that generate swallowing are still largely unknown. It has been suggested that a central pattern generator that contains a serial network of linked neurons must produce the successive excitation of motoneurons (Mns) and then the sequential activation of muscle through excitatory connections. Inhibitory connections have also been envisioned but never evidenced at the membrane level of the swallowing neurons. We investigated, by intracellular recordings, the behavior of 96 Mns in the rostral nucleus ambiguus during swallowing induced by application of superior laryngeal nerve stimulation to anesthetized sheep. The Mns were identified by antidromic activation following stimulation of glossopharyngeal, pharyngoesophageal, or cervical vagal nerves. Nine Mns showed a bell-shaped depolarization during the buccal or the early pharyngeal stage of swallowing. They probably projected to muscles of the soft palate (palatopharyngeal) and upper pharynx (stylopharyngeal, hyopharyngeal). Thirty-eight Mns exhibited a chloride-dependent hyperpolarization, indicating that they were under an active inhibition throughout the buccopharyngeal stage of swallowing. These Mns constitute a heterogeneous pool: some of them, producing spontaneous inspiratory discharges, probably innervated laryngeal or pharyngeal muscles; others might also be Mns of the esophagus, whose swallowing pattern was modified because of the anesthesia (suppression of the esophageal peristalsis). Forty-nine Mns showed a chloride-dependent hyperpolarization with a variable duration at the onset of swallowing, followed by a depolarization that could take place during either the buccopharyngeal (HD1-Mns) or the esophageal (HD2- and HD3-Mns) stage of deglutition. HD1-Mns probably projected to the median and inferior constrictors of the pharynx. HD2-Mns produced depolarizations with longer latencies and durations than those of the HD1-Mns. They probably projected to either the superior esophageal sphincter or the cervical esophagus (CE). HD3-Mns showed a buccopharyngeal hyperpolarization that was followed first by a lower-amplitude hyperpolarization accompanying the proximal CE contraction and then by a delayed depolarization. These Mns probably innervated the inferior CE or thoracic esophagus. We conclude that the initial inhibition exerted on the HD-Mns, by delaying the excitation of Mns, may play a role in the nervous mechanisms involved in temporal organization of the swallowing motor sequence. We suggest that swallowing disorders in humans such as dysphagia by failure of cricopharyngeal relaxation, diffuse esophageal spasm, and achalasia might be caused by impaired inhibitory mechanisms.

Animals↗

PubMed1997

Adrenomedullin increases pulmonary blood flow in fetal sheep.

We studied the effects of exogenously administered adrenomedullin on fetal pulmonary arterial blood flow in near-term fetal sheep. The hemodynamic effects of a single injection of adrenomedullin into the left pulmonary artery were compared with those of acetylcholine; the effects of repeated injections of adrenomedullin were also studied. In seven unanesthetized fetal sheep, catheters were inserted into the left pulmonary artery to administer drugs, and into the main pulmonary and carotid arteries to measure pressures. An ultrasonic flow transducer was placed around the left pulmonary artery to measure flow continuously. A single 5-microgram injection of adrenomedullin (1.90 +/- 0.35 micrograms/kg of fetal weight) increased pulmonary arterial blood flow significantly, from 17 +/- 10 to 120 +/- 21 mL/min (p < 0.001). Two micrograms of acetylcholine (0.74 +/- 0.14 microgram/kg of fetal weight) also increased left pulmonary arterial blood flow, from 18 +/- 16 to 113 +/- 37 mL/min, but the effect of adrenomedullin on flow was more prolonged than was that of acetylcholine. Additionally, adrenomedullin and acetylcholine similarly decreased mean pulmonary arterial pressure by 11 and 16%, respectively, but adrenomedullin did not decrease mean carotid arterial pressure to the same degree as acetylcholine (2 versus 19%, respectively). Five sequentially repeated injections of adrenomedullin, once every 5 min, increased left pulmonary arterial blood flow significantly in a stepwise manner without significantly changing heart rate or mean pulmonary and carotid arterial pressures. We conclude that exogenously administered adrenomedullin is a pulmonary vasodilator in fetal sheep and has the ability to increase pulmonary blood flow significantly; there is less effect on the systemic circulation. This finding might be important in considering the therapeutic use of this peptide in the management of persistent pulmonary hypertension in the perinatal period.

Acetylcholine↗

PubMed1997

Perinatal regulation of the cerebral circulation: role of nitric oxide and prostaglandins.

Nitric oxide (NO) influences cerebral vascular tone both in the normal fetus and in the hypoxemic fetus, but during postnatal life this regulating role of NO seems less prominent. It is therefore possible that under conditions when arterial oxygen content is at postnatal levels NO exerts no action on smooth muscle. We therefore examined the impact of NO on cerebral blood flow and vascular resistance in five near-term lamb fetuses during intrauterine ventilation and oxygenation. Four additional fetuses were pretreated with indomethacin to investigate a possible additional regulatory role of prostaglandins on cerebral vascular resistance. Cerebral blood flow (Qbrain) was measured using radionuclide-labeled microspheres. A tracheal tube was inserted to ventilate the fetus. After recovery, Qbrain and resistance in the cerebral vascular bed (Rcer) were measured during the following subsequent conditions: before and after increasing fetal arterial O2 content by ventilation with air, after inhibition of NO production with N(omega)-nitro-L-arginine during and after cessation of ventilation, and finally after infusion of L-arginine to increase nitric oxide production. Ventilation decreased Qbrain (95 +/- 18 to 47 +/- 15 mL/100 g/min) and increased Rcer. N(omega)-Nitro-L-arginine did not alter Qbrain (52 +/- 13 mL/100 g/min) or Rcer during ventilation and oxygenation, indicating no modulating role of NO during higher arterial oxygen content. On cessation of ventilation, PO2 returned to fetal levels and Qbrain increased significantly, but did not return to baseline fetal values (83 +/- 7 mL/min). Infusion of L-arginine increased Qbrain to baseline fetal levels (116 +/- 30 mL/min). However, indomethacin pretreatment prevented the rise in cerebral blood flow after cessation of ventilation and after additional L-arginine infusion (Qbrain 53 +/- 20 and 52 +/- 4 mL/100 g/min. respectively). These studies indicate that, during postnatal levels of arterial oxygen content, NO does not exert an action on smooth muscle cells of the cerebral resistance vessels as it does at lower arterial (fetal) oxygen content. They further show that prostaglandins are important in facilitating the full expression of NO-induced vasodilation.

Animals↗

PubMed1995

Role of nitric oxide in the regulation of the cerebral circulation in the lamb fetus during normoxemia and hypoxemia.

The influence of nitric oxide (NO) blockade on resting tone and on hypoxia-induced vasodilatation of the cerebral vascular bed was examined in chronically instrumented lamb fetuses. Total (Qbrain-tot) and regional brain blood flow were measured using radioactive microspheres. NO blockade was achieved by N omega-nitro-L-arginine (NNLA) infusion into the carotid artery via a lingual artery. Fetal cerebral blood flow and cerebral vascular resistance (Rcer) were determined during normoxemia and hypoxemia and before and during infusion of L-arginine. During normoxemia, the brain blood flow decreased, and the resistance increased significantly after NNLA infusion (Qbrain-tot from 129 +/- 25 to 89 +/- 26 ml/100 g/min, p < 0.05; Rcer from 0.46 +/- 0.03 to 0.80 +/- 0.09 mm Hg/ml/100 g/min, p < 0.05). During hypoxemia before NNLA infusion, Qbrain-tot increased (from 129 +/- 25 to 187 +/- 56 ml/100 g/min, p < 0.05), and Rcer decreased (from 0.46 +/- 0.03 to 0.39 +/- 0.07 mm Hg/ml/100 g/min, p < 0.05). This vasodilatory response was largely blocked after NNLA (Qbrain-tot 143 +/- 45 ml/100 g/min; Rcer 0.58 +/- 0.07 mm Hg/ml/100 g/min). The response to hypoxemia was restored after infusion of L-arginine (Qbrain-tot 180 +/- 47 ml/100 g/min). The resting tone of the cerebral vascular bed of the lamb fetus is under NO control, and NO mediates the cerebral vasodilatory response to hypoxia in the lamb fetus.

Animals↗

PubMed1994

Limited expression of C/EBP family proteins during B lymphocyte development. Negative regulator Ig/EBP predominates early and activator NF-IL-6 is induced later.

The importance of C/EBP proteins in B cell biology is suggested by the occurrence of functionally important C/EBP binding sites in Ig gene enhancers and promoters, and the knowledge that family member NF-IL-6 is induced in other systems in response to regulators of B cell differentiation. We have studied the expression pattern and activity of C/EBP family transcriptional regulators in B cells at different developmental stages by using B cell lines and normal splenic B cells. Two family members, Ig/EBP and NF-IL-6, seem to be the major regulators of C/EBP site-dependent transcriptional activity in B cells. Negative regulator Ig/EBP is predominantly present in early B cells; activator NF-IL-6 increases in more mature B cells and is induced by LPS activation of splenic B cells. LIP, an N-terminally truncated form of NF-IL-6, was found in most B cell lines tested; LIP can act as a weak transcriptional activator in B cell lines. Partly as a result of the differential amounts of C/EBP family proteins, C/EBP sites do not function as activator sites in early B cells but are activator sites in terminally differentiated B cells.

Animals↗

PubMed1994

Relationship between brain blood flow and carotid arterial flow in the sheep fetus.

The present study investigates whether changes in total brain blood flow can be reliably estimated by changes in carotid arterial blood flow in fetal and perinatal lambs. We therefore compared carotid arterial blood flow, measured with implanted transit-time ultrasound transducers, with brain blood flow, measured by radioactive microspheres in fetal lambs during normal oxygenation and during pulmonary ventilation with oxygen, with PO2 ranging from levels normal for the healthy fetus to levels normally seen postnatally. Cerebral perfusion pressure was modified over a wide range to alter brain blood flow: it was decreased by balloon occlusion of the brachiocephalic trunk and increased by a balloon occluder around the aortic isthmus. Carotid arterial blood flow and brain blood flow were closely related (r = 0.97, p < 0.0001). The relationship was not altered at different levels of oxygenation. However, measurements during higher cerebral perfusion pressures, obtained during aortic isthmus occlusion, had a negative influence on the agreement between carotid arterial blood flow and brain blood flow. When excluding values obtained by aortic isthmus occlusion, changes of 20% or more in brain blood flow could be predicted with carotid arterial blood flow within a confidence limit of 95%. Blood flow measurements in the carotid artery may be useful to estimate changes in brain perfusion.

Animals↗

PubMed1994

Bradykinin receptor blockade does not affect oxygen-mediated pulmonary vasodilation in fetal lambs.

Both oxygenation and rhythmic stretching of the lungs are factors known to be responsible for pulmonary vasodilation at birth. Based on our previous studies, we proposed that the pulmonary vasodilation caused by oxygen could be mediated, at least in part, through bradykinin release. To test this hypothesis, we evaluated the cardiovascular responses to in utero ventilation during infusion of a B2-subtype bradykinin receptor antagonist (BKA), [N-adamantaneacetyl-D-Arg0,Hyp3,Thi5,8,D-Phe7]bradykinin, at 15-20 micrograms.kg-1.min-1 in eight near-term fetal lambs and during drug vehicle infusion in five control fetal lambs. Prostacyclin synthesis was inhibited by meclofenamate infusion (1.5 mg.kg-1.h-1). Surgical placement of vascular catheters, a flow transducer around the left pulmonary artery, and a tracheostomy tube and formalin infiltration of the ductus arteriosus to maintain its patency in the presence of meclofenamate were performed 72 h before the study. Hemodynamic variables and pulmonary blood flow were measured and pulmonary vascular resistance was calculated before and after in utero ventilation with 100% oxygen. Despite complete blockade by BKA of the pulmonary vasodilation produced by exogenous bradykinin, ventilation with oxygen significantly increased pulmonary blood flow by 676% over baseline state (157.8 +/- 66 to 1224 +/- 265 mL.min-1.100 g-1, p < 0.01) and decreased the pulmonary vascular resistance by 89% from baseline state (0.44 +/- 0.16 to 0.048 +/- 0.01 torr.mL-1.min.100 g, p < 0.01). Such responses to ventilation with oxygen were comparable to those noted in the control animals, in whom bradykinin receptors had not been blocked.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1993

Enkephalin-containing neurons in the inferior mesenteric ganglion projecting to the distal colon of cat: evidence from combined retrograde tracing by fluorescent microspheres and immunohistochemistry.

Retrograde tracing with rhodamine fluorescent microspheres combined with fluorescein immunolabelling of methionine-enkephalin showed the presence of enkephalin-like material in neurons of the inferior mesenteric ganglion (sympathetic prevertebral ganglion) projecting to the distal colon in cat. Two weeks after injecting the microspheres into the wall of the distal colon, the inferior mesenteric ganglion was dissected out and incubated for 24 hours in a colchicine-containing culture medium in order to facilitate the detection of enkephalins in the soma of ganglion neurons. It was observed that retrogradely labelled ganglion cells contained enkephalin-like immunoreactive material. These ganglion cells corresponded to enkephalin-like postganglionic neurons, the terminals of which were located inside the wall of the distal colon. These enkephalin-like neurons were numerous and scattered throughout the ganglion. Sometimes enkephalin-like immunoreactive fibers, probably originating from spinal preganglionic neurons, ran close to immunoreactive and non-immunoreactive retrogradely labelled ganglion cells. This suggests that enkephalin-like immunoreactive fibers may make synaptic connections with enkephalin-like and non-enkephalin-like postganglionic neurons projecting to the distal colon. The present study establishes for the first time the existence of an enkephalin-like postganglionic pathway to the digestive tract originating from a sympathetic prevertebral ganglion. This finding indicates that the enkephalinergic innervation of the cat digestive tract may have at least two possible sources: (i) the sympathetic prevertebral ganglia; and (ii) the enteric nervous ganglia.

Animals↗

PubMed1993

Sympathoadrenal, metabolic, and regional blood flow responses to cold in fetal sheep.

Because environmental temperature falls when the fetus is delivered from the uterus, the role of cold in stimulating cardiovascular and sympathoadrenal responses at the time of birth was examined in fetal lambs. In eight fetuses (gestational age 140 +/- 2 d), catheters were inserted into hind-limb and neck arteries and veins, and into an umbilical vein. After returning the fetus to the uterus and administering a muscle relaxant (succinylcholine chloride), blood gases, glucose and lactate concentrations, and plasma catecholamine and atrial natriuretic peptide concentrations were measured. Fetal combined ventricular output and organ blood flows were measured by the radionuclide-labeled microsphere technique. Measurements were repeated after delivering the fetus into a warm water bath (40 degrees C) and at 15 and 30 min after the bath temperature was cooled to 25 degrees C. Fetal cooling stimulated a sympathoadrenal response, which was manifested by an immediate increase in heart rate and arterial blood pressure, a rise in atrial natriuretic peptide, and modest increase in norepinephrine concentration. Contrary to earlier reports that investigated the effect of cold on fetal lambs using an intrauterine cooling coil, we did not find a decrease in fetal arterial oxygen tensions and pH, an increase in plasma glucose and lactate concentrations, or changes in fetal oxygen consumption. Combined ventricular output did not increase with cooling, and blood flow to most organs did not change significantly; however, blood flow to the skin decreased markedly, particularly in the lower body.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

PubMed1992

The C/EBP family of transcriptional activators is functionally important for Ig VH promoter activity in vivo and in vitro.

We have examined the functional importance of binding sites for C/EBP family members (E sites), in two Ig VH promoters: VH1, a member of the S107 family, and BCL1, a member of the J558 family. Mutation of the E site in the VH1 promoter diminishes transcription in vivo to 59% of wild-type and transcription from the BCL1 promoter in vitro is inhibited to an average of 39% of wild-type by competition with E site oligonucleotides. Purified E site binding proteins from plasmacytoma cells stimulated BCL1 transcription in vitro 2.3-fold. Although five C/EBP family proteins are known which bind the E site, antibody ablation of DNA:protein complexes resolved by electrophoretic mobility shift assays showed that Ig/EBP-1 is the only E site binding protein detectable in early B cell lines; more mature B cells contain Ig/EBP-1 and NF-IL6. We also show by antibody-depletion that Ig/EBP-1 activates the BCL1 promoter in vitro.

Animals↗

PubMed1992

Effect of endothelium-derived relaxing factor inhibition on the umbilical-placental circulation in fetal lambs in utero.

OBJECTIVE: The purpose of this study was to examine whether basal endothelium-derived relaxing factor release contributes to regulation of resting umbilical-placental vascular resistance. STUDY DESIGN: Because N omega-nitro-L-arginine selectively inhibits the synthesis of nitric oxide, a major endothelium-derived relaxing factor, we investigated the effects of N omega-nitro-L-arginine on umbilical-placental vascular resistance in 10 fetal lambs in utero. We inserted catheters and fitted an umbilical artery electromagnetic flow transducer around the common umbilical artery to measure umbilical blood flow and catheterized the left umbilical arterial hypogastric branch to allow selective umbilical-placental infusion (60 minutes) of pH-matched saline solution (control) or N omega-nitro-L-arginine. RESULTS: In seven normal fetal lambs, N omega-nitro-L-arginine increased umbilical-placental vascular resistance and arterial pressures and decreased umbilical blood flow (p less than 0.05); percentage changes from baseline were 50.8% +/- 18.3%, 40.3% +/- 8.1%, and -9.9% +/- 6.4%, respectively. In three mildly asphyxiated (compromised) fetuses, these changes were 101.4% +/- 28.7%, 31.2% +/- 4.8%, and -37.9% +/- 12.0%. CONCLUSION: These data support the hypothesis that the basal endothelium-derived relaxing factor release plays a role in regulating resting umbilical-placental vascular resistance.

Animals↗

PubMed1992

mTFE3, an X-linked transcriptional activator containing basic helix-loop-helix and zipper domains, utilizes the zipper to stabilize both DNA binding and multimerization.

Southwestern (DNA-protein) screening of a murine L-cell cDNA library by using a probe for the microE3 site in the immunoglobulin heavy-chain enhancer yielded a clone, mTFE3, which is a member of the subset of basic helix-loop-helix (BHLH) proteins that also contain a leucine zipper (ZIP). Since the individual contribution of these domains is not well understood for proteins which contain them both, mutational analyses were performed to assess the functional roles of the HLH and ZIP regions for DNA binding and multimerization. The HLH region is stringently required for DNA binding but not for multimerization. The ZIP region is not stringently required for binding or multimerization, but stabilizes both multimer formation and DNA binding. A high degree of conservation at both the amino acid and nucleotide levels between the human transcription factor TFE3 and mTFE3 suggests that mTFE3 is the murine homolog of human TFE3. By using fluorescent in situ hybridization, mTFE3 was mapped to mouse chromosome X in band A2, which is just below the centromere. We show that in addition to the immunoglobulin heavy-chain microE3 site, mTFE3 binds to transcriptional elements important for lymphoid-specific, muscle-specific, and ubiquitously expressed genes. Binding of mTFE3 to DNA induces DNA bending.

Amino Acid Sequence↗

PubMed1992

Platelet-induced thrombin generation time: a new sensitive global assay for platelet function and coagulation. Method and first results.

A new sensitive test--platelet-induced thrombin generation time (PITT)--is described, in which the formation of thrombin in partially anticoagulated platelet-rich plasma (PRP) leads to aggregation immediately followed by coagulation of PRP. 0.6 ml PRP are rotated in a disk-shaped cuvette within the light beam of a photometer. In PITT, platelets stick to the cuvette wall and, mediated by a large PRP/surface/air interface at the cuvette wall, are activated and participate in thrombin formation which leads to aggregation and clotting. The times from onset of rotation until aggregation (Ta) and until coagulation (Tc) of the PRP samples are recorded. PITT was very sensitive and detected low concentrations of unfractionated heparin (0.01 IU/ml) in vitro. PITT parameters were significantly prolonged ex vivo 2 h after oral administration of acetylsalicylic acid (0.5 g) and after single subcutaneous injections of heparin (5,000 IU). Patients receiving phenprocoumon prophylaxis had markedly prolonged Ta and Tc values (longer than 20 min, n = 23). Patients with recent thrombotic episodes had markedly shorter values than healthy volunteers. PITT may become a very sensitive global test to detect mild hemorrhagic disorders, to monitor the effects of antithrombotic drugs and to detect patients with a risk of vascular occlusions.

Adult↗

PubMed1992

Amino acid gradients across the intestinal circulation in fetal lambs.

Amino acids, including glutamine, glutamate and asparagine are major metabolic substrates for the adult enterocyte of several species. To determine whether circulating amino acids are utilized by the fetal intestine, we studied nine fetal sheep (mean gestational age 128 +/- 5 days; term: 147 days). Catheters were inserted into the descending aorta (DA) and the mesenteric vein (MV) to allow for simultaneous blood sampling across the intestine. Fetal blood gas, haemoglobin; O2 saturation and O2 tension were measured. Ammonia was determined by an enzymatic method and HPLC analysis was used to measure the content of all amino acids in DA (descending aorta) and MV (mesenteric vein). Intestinal blood flow measurements were obtained using the radionuclide microsphere method. Intestinal blood flow (81 +/- 28 ml/min/100g) and arterial pH (7.37 +/- 0.04) were within normal range for unstressed fetal lambs. Glutamine and glutamate were the only amino acids that were significantly taken up across the fetal intestinal circulation. The fetal intestine extracted approximately 21% of the delivered glutamine (6.8 +/- 4.5 mumol/min/100g), 7% of the delivered glutamate (1.3 +/- 1.1 mumol/min/100g) and 2.7% of the delivered oxygen (43.0 +/- 19.1 mumol/min/100g). These data suggest that glutamine and glutamate are major substrates for the intestine in unstressed fetal lambs.

Alanine↗