Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “REST”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 631 records · Page 35Linked to original sources
PubMed2002

Tissue temperature transients in resting contra-lateral leg muscle tissue during isolated knee extension.

This study was designed to evaluate the role of non-active tissue in the retention and dissipation of heat during and following intense isolated muscle activity. Six subjects performed an incremental isotonic test (constant angular velocity, increases in force output) on a KIN-COM isokinetic apparatus to determine their maximal oxygen consumption during single knee extensions (VO2sp). In a subsequent session, a thin wire multi-sensor temperature probe was inserted into the left vastus medialis under ultrasound guidance at a specific internal marker. The deepest temperature sensor (tip, Tmu10) was located approximately 10 mm from the femur and deep femoral artery with 2 additional sensors located at 15 (Tmu25) and 30 (Tmu40) mm from the tip. Implant site was midway between and medial to a line joining the anterior superior iliac spine and base of patella. Esophageal temperature (Tes) temperature was measured as an index of core temperature. Subjects rested in a supine position for 60 min followed by 30 min of seated rest in an ambient condition of 22 degree C. Subjects then performed 15 min of isolated single right knee extensions against a dynamic resistance on a KIN COM corresponding to 60% of VO2sp at 60 degree x sec(-1). Exercise was followed by 60 min of seated rest. Resting Tes was 37 degree C while Tmu10, Tmu25, and Tmu40 were 36.58, 36.55 and 36.45 degree C, respectively. Exercise resulted in a Tes increase of 0.31 C above pre-exercise resting. Tmu of the non-exercising leg increased 0.23, 0.19 and 0.09 degree C for Tmu10, Tmu25, and Tmu40, respectively. While Tes decreased to baseline values within approximately 15 min of end-exercise, Tmu10 reached resting values following approximately 40 min of recovery. These results suggest that during isolated muscle activity, convective heat transfer by the blood to non-active muscle tissue may have a significant role in maintaining resting core temperature.

Adult↗
PubMedDate not supplied

Nephrogenic rests, nephroblastomatosis, and associated lesions of the kidney.

The fetal kidney is formed by the development of nephrons from fetal metanephric blastema surrounding the ureteric bud. The fetal renal tissue matures into normal renal parenchyma during gestation, but, occasionally, fetal tissue persists into infancy as microscopic foci called nephrogenic rests. Nephrogenic rests are found in approximately 1% of infant kidneys at autopsy. Nephrogenic rests are associated with an increased risk of Wilms tumor, and it is theorized that nephrogenic rests undergo neoplastic change into Wilms tumor. Fortunately, this transformation occurs in less than 1% of young children with nephrogenic rests. Nephrogenic rests are associated with many syndromes, including Beckwith-Wiedemann syndrome, hemihypertrophy, and sporadic aniridia. Children with identifiable syndromes, once diagnosed, should be screened for the development of Wilms tumor. Nephrogenic rests are associated with other lesions such as multilocular cystic nephroma and multicystic dysplasia, usually without malignant complications.

Beckwith-Wiedemann Syndrome↗
PubMed2006

Elevated resting [Ca(2+)](i) in myotubes expressing malignant hyperthermia RyR1 cDNAs is partially restored by modulation of passive calcium leak from the SR.

Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle triggered in susceptible individuals by inhalation anesthetics and depolarizing skeletal muscle relaxants. This syndrome has been linked to a missense mutation in the type 1 ryanodine receptor (RyR1) in more than 50% of cases studied to date. Using double-barreled Ca(2+) microelectrodes in myotubes expressing wild-type RyR1 ((WT)RyR1) or RyR1 with one of four common MH mutations ((MH)RyR1), we measured resting intracellular Ca(2+) concentration ([Ca(2+)](i)). Changes in resting [Ca(2+)](i) produced by several drugs known to modulate the RyR1 channel complex were investigated. We found that myotubes expressing any of the (MH)RyR1s had a 2.0- to 3.7-fold higher resting [Ca(2+)](i) than those expressing (WT)RyR1. Exposure of myotubes expressing (MH)RyR1s to ryanodine (500 microM) or (2,6-dichloro-4-aminophenyl)isopropylamine (FLA 365; 20 microM) had no effects on their resting [Ca(2+)](i). However, when myotubes were exposed to bastadin 5 alone or to a combination of ryanodine and bastadin 5, the resting [Ca(2+)](i) was significantly reduced (P < 0.01). Interestingly, the percent decrease in resting [Ca(2+)](i) in myotubes expressing (MH)RyR1s was significantly greater than that for (WT)RyR1. From these data, we propose that the high resting myoplasmic [Ca(2+)](i) in (MH)RyR1 expressing myotubes is due in part to a related structural conformation of (MH)RyR1s that favors "passive" calcium leak from the sarcoplasmic reticulum.

Allosteric Regulation↗
PubMed1987

Effects of rest duration and ryanodine on changes of extracellular [Ca] in cardiac muscle from rabbits.

Cumulative depletions of extracellular Ca were measured using double-barreled Ca-sensitive microelectrodes in the extracellular space of rabbit ventricular muscle. Depletions were produced by 1-Hz stimulation after rest intervals of 10 s to 10 min. With longer rest intervals, depletion size increased while the first postrest contraction decreased in a reciprocal manner. The depletions may represent refilling of sarcoplasmic reticulum (SR) Ca stores that have become partially depleted of Ca during the rest. Within this interpretive framework, the longer the rest interval the lower the SR Ca content, so the SR is then capable of taking up larger amounts of Ca. This may be related to the rest decay of tension of the first postrest beat, since this is thought to be SR dependent. Ryanodine (1 microM) increased the size of the depletions after short rest intervals (less than 2 min) but not after longer (greater than or equal to 2 min) intervals. Ryanodine also increased the rate of Ca loss from the cell on cessation of stimulation. This increased rate of Ca loss with ryanodine may deplete the SR of Ca such that more Ca can be taken up during subsequent stimulation than in untreated muscles. Thus cumulative depletions after short rest intervals are enhanced by ryanodine. When a Ca load was produced during 1) quiescence [by removal of extracellular Na (Nao)] or 2) continuous stimulation (in the presence of 3 microM acetylstrophanthidin), addition of ryanodine (5-10 microM) did not produce any apparent Ca loss. Caffeine (10 mM), added after ryanodine, induced contractures accompanied by Ca efflux, implying there was Ca in the SR after ryanodine exposure. The results of other investigators have suggested that ryanodine may inhibit cardiac SR Ca release. The present study suggests that ryanodine also enhances the loss of cellular (and probably SR) Ca on cessation of stimulation but not when applied during continuous stimulation or quiescence.

Alkaloids↗
PubMed1995

Resting load regulates vascular sensitivity by a cytosolic Ca(2+)-insensitive mechanism.

The cellular mechanism underlying the regulation of the contraction of vascular smooth muscles by resting load is unknown. To determine the effects of changes in the resting load on vascular sensitivity to high K+ and to 9,11-dideoxy-11 alpha, 9 alpha-epoxy-methanoprostaglandin F2 alpha (U-46619), the force and cytosolic calcium concentration ([Ca2+]i) of arterial strips were recorded at resting loads of 200 (optimal load), 50, and 10 mg. A decrease in the resting load elicited a small decrease in the basal [Ca2+]i level without affecting the extent of maximal [Ca2+]i elevation induced by either stimulus. Through a decrease in the resting load, the concentration-response curves for the force development of high K+ or of U-46619 shifted to the right, whereas those for [Ca2+]i did not. We conclude that the basal [Ca2+]i level and the force development, but not the agonist-induced [Ca2+]i signals, of vascular smooth muscles depend on the resting load. We response that the resting load regulates the sensitivity of vascular smooth muscles, irrespective of types of stimuli, through a [Ca2+]i-insensitive mechanism.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1993

Lactate is essential for maintenance of euglycemia in iron-deficient rats at rest and during exercise.

To evaluate the hypothesis that lactate supply is essential to maintain euglycemia during iron deficiency, female Sprague-Dawley rats were assigned to iron-sufficient (50 mg Fe2+/kg diet, +Fe), or iron-deficient (15 mg Fe2+/kg diet, -Fe) dietary groups and were injected with a specific beta 2-adrenergic inhibitor, ICI 118,551 (1.0 mg/kg body wt). Rats were studied at rest or after 30 min of running at 13.4 m/min 0% grade. Dietary iron deficiency decreased hemoglobin concentration 38%, but resting arterial concentrations of glucose ([Glc]), lactate ([La]), or alanine ([Ala]) were unaffected. Administration of ICI 118,551 (beta 2-blockade) decreased [La] and [Glc] 52 and 32% in resting -Fe rats, respectively. beta 2-Blockade attenuated the exercise-induced rise in [La] and decreased [Glc] 31% in exercising -Fe rats. [Ala] were unaffected by iron deficiency or exercise but decreased 24 and 18% because of beta 2-blockade in resting and exercising +Fe rats. Iron deficiency depleted resting liver glycogen concentration 45%, with no additional effect of exercise or beta 2-blockade. beta-Blockade decreased arterial insulin and increased arterial glucagon concentrations in resting -Fe and +Fe rats. During exercise glucagon concentration increased significantly more in -Fe than +Fe rats. Decreased arterial [La] with a corresponding decrease in arterial [Glc] in response to beta 2-blockade support the contention that lactate supply is critical to maintenance of euglycemia in -Fe rats at rest and during exercise.

Adrenergic beta-Antagonists↗
PubMed1981

Twitch potentiation by rest in canine ventricular muscle: effects of theophylline.

Short rest of the regular stimulation of the isolated canine right ventricular muscle induced a large transient increase of subsequent twitch tension (rest-twitch potentiation, RTP). This RTP attained the maximum level when the rest period was 120 s and decayed progressively at longer rest periods. The rate of regular stimulation prior to rest affected the degree of RTP but not the time course of RTP. The action potential duration was prolonged progressively after rest until 120 s and maintained this level at longer rest periods. Under the same experimental condition, RTP was not induced in the rabbit papillary muscle. Theophylline, caffeine, and epinephrine increased the strength of steady-state contraction, whereas RTP was inhibited by theophylline and caffeine and unaffected by epinephrine. Manganese and D 600 significantly reduced the strength of steady-state contraction but did not affect the degree of RTP. These results indicate that RTP is induced via a mechanism different from that regulating the steady-state contraction.

Action Potentials↗
PubMed1993

Functional role of Ca(2+)-activated K+ channels in resting state of carotid arteries from SHR.

Carotid arteries from spontaneously hypertensive rats (SHR) exhibited an active tone when exposed to a physiological salt solution; that is, the tension decreased when nifedipine was added. To determine the possible role of Ca(2+)-activated K+ (KCa) channels in the resting state of these arteries, the effects of agents that interact with these channels on tension and 86Rb efflux were compared in endothelium-denuded strips of carotid arteries from SHR and normotensive Wistar-Kyoto rats (WKY). The addition of charybdotoxin, a blocker of high-conductance KCa channels, to the resting strips produced a concentration-dependent contraction in SHR but not in WKY. In resting strips preloaded with 86Rb, the basal 86Rb efflux rate constant was significantly greater in SHR than in WKY. The addition of nifedipine to the resting strips decreased the basal 86Rb efflux rate constant only in SHR. The effect of nifedipine on tension and 86Rb efflux in 25.9 mM K(+)-contracted strips of WKY was comparable to the effect of this blocker in the resting strips of SHR. The basal 45Ca influx in resting strips of SHR was significantly increased when compared with WKY, and this increase in SHR was abolished by nifedipine. These results suggest that the transmembrane Ca2+ influx via L-type voltage-dependent Ca2+ channels was significantly increased in the resting state of carotid arteries from SHR and that the KCa channels were highly activated.

Animals↗
PubMed1998

Role of adenosine in the regulation of coronary blood flow in swine at rest and during treadmill exercise.

A pivotal role for adenosine in the regulation of coronary blood flow is still controversial. Consequently, we investigated its role in the regulation of coronary vasomotor tone in swine at rest and during graded treadmill exercise. During exercise, myocardial O2 consumption increased from 167 +/- 18 micromol/min at rest to 399 +/- 27 micromol/min at 5 km/h (P </= 0.05), which was paralleled by an increase in O2 delivery, so that myocardial O2 extraction (76 +/- 1 and 78 +/- 1% at rest and 5 km/h, respectively) and coronary venous PO2 (24.5 +/- 1.0 and 22.8 +/- 0.3 mmHg at rest and 5 km/h, respectively) remained unchanged. After adenosine receptor blockade with 8-phenyltheophylline (5 mg/kg iv), the relation between myocardial O2 consumption and coronary vascular resistance was shifted toward higher resistance, whereas myocardial O2 extraction rose to 81 +/- 1 and 83 +/- 1% at rest and 5 km/h and coronary venous PO2 fell to 19.2 +/- 0.8 and 18.9 +/- 0.8 mmHg at rest and 5 km/h, respectively (all P </= 0.05). Thus, although adenosine is not mandatory for the exercise-induced coronary vasodilation, it exerts a vasodilator influence on the coronary resistance vessels in swine at rest and during exercise.

Adenosine↗
PubMed2000

Effect of head-down-tilt bed rest and hypovolemia on dynamic regulation of heart rate and blood pressure.

Adaptation to head-down-tilt bed rest leads to an apparent abnormality of baroreflex regulation of cardiac period. We hypothesized that this "deconditioning response" could primarily be a result of hypovolemia, rather than a unique adaptation of the autonomic nervous system to bed rest. To test this hypothesis, nine healthy subjects underwent 2 wk of -6 degrees head-down bed rest. One year later, five of these same subjects underwent acute hypovolemia with furosemide to produce the same reductions in plasma volume observed after bed rest. We took advantage of power spectral and transfer function analysis to examine the dynamic relationship between blood pressure (BP) and R-R interval. We found that 1) there were no significant differences between these two interventions with respect to changes in numerous cardiovascular indices, including cardiac filling pressures, arterial pressure, cardiac output, or stroke volume; 2) normalized high-frequency (0.15-0.25 Hz) power of R-R interval variability decreased significantly after both conditions, consistent with similar degrees of vagal withdrawal; 3) transfer function gain (BP to R-R interval), used as an index of arterial-cardiac baroreflex sensitivity, decreased significantly to a similar extent after both conditions in the high-frequency range; the gain also decreased similarly when expressed as BP to heart rate x stroke volume, which provides an index of the ability of the baroreflex to alter BP by modifying systemic flow; and 4) however, the low-frequency (0.05-0.15 Hz) power of systolic BP variability decreased after bed rest (-22%) compared with an increase (+155%) after acute hypovolemia, suggesting a differential response for the regulation of vascular resistance (interaction, P < 0.05). The similarity of changes in the reflex control of the circulation under both conditions is consistent with the hypothesis that reductions in plasma volume may be largely responsible for the observed changes in cardiac baroreflex control after bed rest. However, changes in vasomotor function associated with these two conditions may be different and may suggest a cardiovascular remodeling after bed rest.

Adult↗
PubMed1979

Plasma volume changes during rest and exercise in different postures in a hot humid environment.

Plasma volume shifts were investigated in five male subjects who rested and exercised in the upright, low-sit, and supine postures in a hot humid environment (49.5 degrees C, 28.9 Torr). The resting and exercise periods were each 45 min in duration. Weight losses during rest were 0.3% with an additional weight loss of 1.1% during exercise. During exercise subjects worked at either 360 or 540 kpm.min-1 in each of three postures. Each experiment was preceded by a 30-min control period in the supine posture at an ambient temperature of 22 degrees C. At rest plasma volume was reduced 17.3% in the upright, 9.0% in the low-sit, and 2.2% in the supine postures (using the end of the supine rest as the zero reference point). Supine exercise resulted in a plasma volume decrease of 11%, the low-sit 7.1%, and the upright 2.7%. The total reduction in plasma volume during the rest and exercise period was 20% in the upright, 16.1% in the low-sit, and 13.3% in the supine. No significant differences in plasma volume shifts were observed between the high and low work loads. The results indicate that the plasma volume shifts observed during rest and exercise in the heat are qualitatively similar to those observed in a cool environment.

Adult↗
PubMed1998

Resting membrane properties of locust muscle and their modulation I. Actions of the neuropeptides YGGFMRFamide and proctolin.

The resting K+ conductance (GK,r) of locust jumping muscle and its modulation by two neuropeptides, proctolin (Arg-Tyr-Leu-Pro-Thr) and YGGFMRFamide (Tyr-Gly-Gly-Phe-Met-Arg-Phe-NH2), were investigated using the two-electrode voltage clamp. At a physiological [K+]o of 10 mM, GK,r accounts for approximately 90% of the membrane resting conductance, and the resting membrane potential differs by </=1 mV from EK (mean: -74 mV). There is a K+ conductance that slowly activates on hyperpolarization (GK,H) and that seems to be largely located in the transverse tubules. Steady-state activation of GK,H was analyzed by tail current measurements. GK,H is activated partially at EK but accounts for probably </=50% of total resting K+ conductance. Raising [K+]o caused a large increase in GK,r and in maximal steady state GK,H without shifting the voltage sensitivity of GK,H. YGGFMRFamide and proctolin reduce GK,H, mainly affecting the maximal steady-state conductance. The voltage-insensitive component of the resting K+ conductance is also reduced. The conductance suppressed by the peptides exhibited an outwardly rectifying instantaneous current/voltage-characteristic that is quite similar to that of GK,H. The actions of the two peptides appeared to be identical, but proctolin was by some two orders of magnitude more potent than YGGFMRFamide. The effects of both peptides are mediated by G proteins. They are mimicked by phorbol esters but do not seem to be initiated by either branch of the phospholipase C-dependent intracellular pathways. The properties of the resting K+ conductance in locust muscle and other invertebrate muscles are compared. The biological significance of peptide-induced reduction in resting K+ conductance is discussed in view of the known property of proctolin to support tonic force as opposed to FMRFamide-peptides that support quick leg movements.

Animals↗
PubMed1992

Effect of propranolol and disopyramide on left ventricular function at rest and during exercise in hypertrophic cardiomyopathy.

In 19 patients with hypertrophic cardiomyopathy (15 males, 4 females, mean age 49.2 +/- 10.8 years) left ventricular function was studied with radionuclide ventriculography at rest and during exercise in a crossover design without intervention and after disopyramide and propranolol treatment. 15 of the 19 patients had a resting or latent intraventricular gradient of more than 30 mm Hg. Left ventricular function at rest and during exercise was evaluated before medication, 90 min after oral administration of 200 mg disopyramide or 160 mg propranolol and after 3 weeks of oral therapy with disopyramide 200 mg 2 times a day or propranolol 80 mg 4 times a day. After long-term treatment with disopyramide, resting ejection fraction decreased from 72 +/- 12 to 69 +/- 14% (p less than 0.01) and peak ejection rate (PER) decreased from 3.46 +/- 135 to 3.24 +/- 65 end-diastolic volume (EDV).s-1 (p less than 0.01). Peak filling rate (PFR) at rest decreased from 3.01 +/- 0.8 to 2.77 +/- 0.63 EDV.s-1 (p less than 0.05). Time to peak filling rate (TPFR) at rest and during exercise after acute and chronic therapy did not change compared to control values. Acute and long-term administration of propranolol lead to a significant reduction in heart rate at rest and during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1982

Arterial oxygenation and arterial oxygen transport in chronic myocardial failure at rest, during exercise and after hydralazine treatment.

Arterial oxygen transport (cardiac output x arterial oxygen content) may be decreased in heart failure. We studied the determinants of arterial oxygen transport in 15 patients with chronic, severe myocardial failure at rest and during cycle ergometry. During control therapy at rest, arterial oxygen tension was normal (81 +/- 8 mm Hg, mean +/- SD) and increased slightly during exercise (90 +/- 14 mm Hg). During hydralazine therapy at rest, arterial oxygen tension was slightly higher (87 +/- 9 mm Hg) and also increased during exercise (92 +/- 15 mm Hg). Hydralazine did not increase arterial oxygen tension (0.10 greater than p greater than 0.05), but exercise did (p less than 0.02). Arterial oxygen saturation and content were normal and did not change under any condition or treatment. During control therapy at rest, arterial oxygen transport was low (313 +/- 74 ml/min . m2) and remained abnormally low during exercise (434 +/- 124 ml/min . m2). During hydralazine therapy, arterial oxygen transport was higher at rest (457 +/- 100 ml/min . m2) and during exercise (577 +/- 131 ml/min . m2). Hydralazine increased arterial oxygen transport (p less than 0.01) because it increased stroke volume at rest and during exercise, but it did not change arterial oxygenation. Arterial oxygenation is normal in chronic heart failure patients at rest and during exercise. Hydralazine increases cardiac output and arterial oxygen transport without changing arterial oxygenation.

Aged↗
PubMed1979

Sarcomere length-resting tension relation in single frog atrial cardiac cells.

It generally has been thought that the relatively high resting tension characteristic of cardiac tissue resides in structures (collagen, elastin) external to the individual cardiac cells, but the evidence to support this conclusion has been indirect, since the resting tension of intact single cardiac cells has not been determined previously. The purpose of the present investigation was to determine the resting tension (stress)-sarcomere length relationships of single intact frog atrial cells. For tension determinations, a single cell was attached between two poly-L-lysine coated glass beams; one beam served as a compliant calibrated cantilevered force beam, and length changes were imposed on the cell by movement of the other beam. Coventional bright-field light microscope techniques were used to view the cell, the sarcomere pattern within the cell, and the position of the force beam. The resting tension of the intact cell increased from a value of about 10 nN at a sarcomere length of 2.35 microns to a value of about 130 nN at a sarcomere length of 3.45 microns. Lagrangian and Eulerian resting stress-sarcomere length relationships were computed from the resting tension-sarcomere length relationships. The Lagrangian stress increased from a value of about 0.6 mN/mm2 at a sarcomere length of 2.35 microns to a value of about 7 mN/mm2 at a sarcomere length of 3.45 microns. These values of stress are about 8- to 30-fold less than those previously reported for intact frog atrial tissue and indicate that the resting tension of intact frog atrial preparations resides primarily in structures external to the individual cardiac cell.

Animals↗
PubMed1984

Intra- and extracellular potassium activities, acetylcholine and resting potential in guinea pig atria.

Intracellular potassium activity in guinea pig left atria was measured using potassium ion-selective microelectrodes and conventional microelectrodes. The effects of extracellular potassium concentration and acetylcholine on both intracellular potassium activity and the relationship between the resting membrane potential and the potassium equilibrium potential were investigated. Intracellular potassium activity was 102.1 mM in bathing media with a potassium concentration of 5 mM. Neither increasing extracellular potassium concentration to 10 mM nor exposure to acetylcholine (2 x 10(-6) to 10(-3) M) significantly altered intracellular potassium activity. In contrast, intracellular potassium activity decreased to 92.9 mM in 2.5 mM potassium concentration solutions. Resting membrane potential was 18.6, 9.6, and 7.3 mV positive to the potassium equilibrium potential in 2.5, 5, and 10 mM potassium, respectively. Acetylcholine caused a significant hyperpolarization at each extracellular potassium activity, confirming that resting membrane potential was positive to the potassium equilibrium potential. Even after exposure to 10(-3) M acetylcholine, the resting membrane potential apparently remained positive to the potassium equilibrium potential. If potassium accumulates in extracellular clefts during acetylcholine exposure, the calculated potassium equilibrium potentials are too negative, and the resting membrane potential might closely approximate the potassium equilibrium potential under these conditions. Fading of the acetylcholine-induced hyperpolarization and overshoot of the resting membrane potential on washout of acetylcholine were observed and are consistent with an accumulation of potassium during exposure to acetylcholine. In 5.0 mM potassium bathing solution, preparation-to-preparation variability of resting membrane potential can largely be explained by variability of intracellular potassium activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed2004

Mouse strain-dependent heterogeneity of resting limbal vasculature.

PURPOSE: Heterogeneity of the extent of angiogenesis induced by exogenous growth factors may be determined by genetic influences. Because angiogenesis is the formation of new vessels from preexisting ones, strain-related influences on naïve resting limbal vessel phenotype and gene expression were determined in mice having divergently low and high angiogenic responses. METHODS: Resting limbal vessel surface area and density and extent of bFGF-induced corneal angiogenesis were determined in C57BL/6J, BALB/cJ, F1 intercross identical with C57BL/6J X 129S3/SvIM, and 129S3/SvIM mouse strains by quantitative three-dimensional reconstruction confocal microscopy. Strain-related influences on pro- and antiangiogenic gene expression in naïve cornea were determined by quantitative real-time RT-PCR. RESULTS: The strain-dependent rank order of resting limbal vessel surface area and resting vessel density paralleled bFGF-induced neovascularization: 129S3/SvIM > BALB/cJ, F1 > C57BL/6J (P < 0.0006). Pigment epithelium-derived factor (PEDF) was increased more than 67-fold compared to Ang-2 in resting cornea of both C57BL/6J and 129S3/SvIM strains (P < 0.0001; P < 0.0001), suggesting a strongly antiangiogenic environment. The corneas of the C57BL/6J mice demonstrated 1.8-, 1.5-, and 1.7-fold increased mRNA levels for Flt-1, VEGF, and bFGF, respectively (P < 0.02; P < 0.04; P < 0.02); however, TSP-1 expression was increased 2.4-fold compared with 129S3/SvIM (P < 0.0004). CONCLUSIONS: Strain-dependent differences in the resting limbal vessel surface area and density correlated with heterogeneity in the extent of bFGF-induced angiogenesis. Differences in pro- and antiangiogenic gene expression levels in resting cornea may influence vascular limbal phenotype during quiescence and may predict susceptibility to angiogenesis-dependent diseases.

Angiopoietin-2↗
PubMed2006

Comparative sequence analysis reveals an intricate network among REST, CREB and miRNA in mediating neuronal gene expression.

BACKGROUND: Two distinct classes of regulators have been implicated in regulating neuronal gene expression and mediating neuronal identity: transcription factors such as REST/NRSF (RE1 silencing transcription factor) and CREB (cAMP response element-binding protein), and microRNAs (miRNAs). How these two classes of regulators act together to mediate neuronal gene expression is unclear. RESULTS: Using comparative sequence analysis, here we report the identification of 895 sites (NRSE) as the putative targets of REST. A set of the identified NRSE sites is present in the vicinity of the miRNA genes that are specifically expressed in brain-related tissues, suggesting the transcriptional regulation of these miRNAs by REST. We have further identified target genes of these miRNAs, and discovered that REST and its cofactor complex are targets of multiple brain-related miRNAs including miR-124a, miR-9 and miR-132. Given the role of both REST and miRNA as repressors, these findings point to a double-negative feedback loop between REST and the miRNAs in stabilizing and maintaining neuronal gene expression. Additionally, we find that the brain-related miRNA genes are highly enriched with evolutionarily conserved cAMP response elements (CRE) in their regulatory regions, implicating the role of CREB in the positive regulation of these miRNAs. CONCLUSION: The expression of neuronal genes and neuronal identity are controlled by multiple factors, including transcriptional regulation through REST and post-transcriptional modification by several brain-related miRNAs. We demonstrate that these different levels of regulation are coordinated through extensive feedbacks, and propose a network among REST, CREB proteins and the brain-related miRNAs as a robust program for mediating neuronal gene expression.

Cyclic AMP Response Element-Binding Protein↗