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Biomedical subjects

B Lu

Publications and source records attributed to B Lu.

At least 253 records · Page 14Linked to original sources
PubMed1991

Depolarizing stimuli regulate nerve growth factor gene expression in cultured hippocampal neurons.

Although trophic factors and neuronal activity have been implicated in regulating functional synaptic circuits, the relationship of trophic interaction to impulse activity in synaptogenesis remains unclear. Using cultured hippocampus as a model system, we provide direct evidence that depolarization and impulse activity specifically increase nerve growth factor gene expression in neurons. Depolarizing stimuli, such as a high K+ concentration or the Na+ channel agonist veratridine, elicited a 3-fold increase of nerve growth factor mRNA levels in both explant and dissociated cultures. Blockade of depolarization by tetrodotoxin prevented the increase of neuronal nerve growth factor mRNA. Further, nerve growth factor gene expression was stimulated by picrotoxin, a gamma-aminobutyric acid antagonist frequently used to enhance hippocampal neuronal activity. Impulse regulation of trophic gene function may be relevant to developmental synaptogenesis and synaptic strengthening in learning and memory.

Animals↗
PubMed1991

Sexually dimorphic expression of the NGF receptor gene in the developing rat brain.

To define relations between trophic molecules and known sexually dimorphic traits in brain, we examined possible sex differences in nerve growth factor (NGF) and NGF receptor (NGF-R) gene expression in the rat cholinergic basal forebrain (BF)-hippocampal system. Hippocampal NGF mRNA levels did not differ between sexes; in contrast, BF NGF-R mRNA levels were greater in neonatal females than males, paralleling the known dimorphic development of cholinergic enzyme activity. Cerebellar NGF-R mRNA levels were also dimorphic in the neonate, suggesting that sex-specific influences may regulate trophic receptor gene expression in diverse brain systems.

Animals↗
PubMed1991

Solutol HS 15, nontoxic polyoxyethylene esters of 12-hydroxystearic acid, reverses multidrug resistance.

A recently developed non-ionic surfactant called Solutol HS 15 (poly-oxyethylene esters of 12-hydroxystearic acid), with low toxicity in vivo, was shown to reverse completely the multidrug resistance of KB 8-5 and KB 8-5-11 human epidermoid carcinoma cells in vitro but did not potentiate drug toxicity in drug-sensitive KB 3-1 cells. At a concentration of 10% of its own IC50 (mean concentration of drug that causes 50% inhibition of cell growth compared to controls), Solutol HS 15 produced a 35-, 28-, and 42-fold reduction in the resistance of KB 8-5-11 cells to colchicine, vinblastine, and doxorubicin, respectively. Solutol HS 15 was relatively much more potent than the prototypic reversing agent, verapamil, for reversing colchicine resistance, compared to the ability of each agent to reverse colchicine resistance, compared to the ability of each agent to reverse vinblastine resistance. Like verapamil, Solutol HS 15 promoted a 50-fold accumulation of rhodamine 123 in KB 8-5-11 cells, as measured by flow cytometry. Also, Solutol HS 15 and verapamil reduced the efflux of rhodamine 123 from KB 8-5-11 cells previously loaded with rhodamine 123 to a similar low rate. Solutol HS 15 did not affect the transport of alanine or glucose into KB 8-5-11 cells, indicating that its effect upon membrane active transport is not entirely nonspecific. Considering their different structure and different relative potency for reversing colchicine resistance, Solutol HS 15 and verapamil probably reverse multidrug resistance by different mechanisms. Solutol HS 15 merits consideration as a potential therapeutic agent because of its effectiveness for reversing multidrug resistance in vitro and its low toxicity in vivo.

Carcinoma, Squamous Cell↗
PubMed1991

Regulation of NGF gene expression in CNS glia by cell-cell contact.

Nerve growth factor (NGF) gene expression in central nervous system (CNS) glia appears to be associated with active glial growth. To study the underlying molecular mechanisms, we examined the effects of a number of growth-related factors on NGF mRNA expression in glial cultures. Our results suggest that glial membrane interaction, as a consequence of growth, actively inhibits NGF gene expression in CNS glia.

Animals↗
PubMed1991

Localization of the gene for the Wiskott-Aldrich syndrome between two flanking markers, TIMP and DXS255, on Xp11.22-Xp11.3.

The Wiskott-Aldrich syndrome (WAS) is an X-linked recessive genetic disease in which the basic molecular defect is unknown. We previously located the WAS gene between two DNA markers, DXS7 (Xp11.3) and DXS14 (Xp11), and mapped it to the proximal short arm of the human X chromosome (Kwan et al., 1988, Genomics 3:39-43). In this study, further mapping was performed on 17 WAS families with two additional RFLP markers, TIMP and DXS255. Our data suggest that DXS255 is closer to the WAS locus than any other markers that have been previously described, with a multipoint maximum lod score of Z = 8.59 at 1.2 cM distal to DXS255 and thus further refine the position of the WAS gene on the short arm of the X chromosome. Possible locations for the WAS gene are entirely confined between TIMP (Xp11.3) and DXS255 (Xp11.22). Use of these markers thus represents a major improvement in genetic prediction in WAS families.

Chromosome Mapping↗
PubMed1991

A prospective study of changes in right ventricular dP/dt during ventricular tachycardia.

The automatic implantable cardioverter defibrillator (AICD) has significantly decreased mortality in high risk ventricular tachycardia (VT) patients. The AICD provides treatment based on ventricular rate, sometimes leading to high energy shocks in conscious patients with stable VT, or patients with sinus or supraventricular tachycardia. Other physiological parameters, such as maximal positive and negative systolic right ventricular (RV) dP/dt (RV + dP/dtmax, RV - dP/dtmax, respectively), may be included in detection algorithms for future implantable defibrillators. We studied frequency band limited positive and negative RV dP/dtmax before, during, and after 13 episodes of VT lasting at least 40 beats in duration in nine male patients. The mean (+/- SEM) RV + dP/dtmax, dropped by 120 +/- 28 mmHg/sec (P less than 0.001) during the first five beats of VT. RV + dP/dtmax then slowly rose toward baseline levels until a significant overshoot occurred during the first ten beats following VT termination (delta = 234 +/- 58 mmHg/second, P less than 0.002). RV + dP/dtmax correlated poorly with mean arterial pressure (r = 0.32, P greater than 0.1), systolic blood pressure (r = 0.19, P greater than 0.1), and VT cycle length (r = 0.34, P greater than 0.1). Conversely, RV - dP/dtmax rose during the first ten beats of VT (74 +/- 27 mmHg/sec, P greater than 0.05) and then slowly drifted back toward baseline levels. Like RV + dP/dtmax, RV - dP/dtmax overshot baseline levels during the recovery phase (-108 +/- 48 mmHg/sec, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1991

[Determination of megestrol acetate and estradiol valerate in injection of microencapsulated compound megestrol acetate by secondary derivative spectrophotometry].

The paper reports the simultaneous determination of megestrol acetate and estradiol valerate in the injection of microencapsulated compound megestrol acetate by secondary derivative spectrophotometry. The experimental results showed that the average recoveries of the two drugs were 98.8% and 98.0%, respectively, and that the coefficients of variation were 0.71% and 1.81%, respectively.

Capsules↗
PubMed1991

[Three-dimensional measurement of fracture gap motion. Biomechanical study of experimental tibial fractures with anterior clasp fixator and ring fixator].

A computer-linked magnetic motion tracker was used to monitor the six components of elastic fracture motions in cadaver tibia with simulated mid-shaft oblique fractures or segmental defects. The limbs were mounted in a servo-hydraulic load frame and stabilized with an Ilizarov frame or an AO-Unifix external fixator. A cyclic load of 150 or 300 N was applied along the long axis of the tibia. Under 150 N load, elastic displacements ranged up to 1.7 mm and elastic rotations ranged up to 0.6 degrees. Under 300 N load, elastic displacements went up to 3.6 mm and elastic rotations ranged up to 1.5 degrees. Comparison of the two fixators showed that the Ilizarov permitted up to 1.75 times more axial pistoning and up to 4 times more A-P displacement. The AO-Unifix permitted up to 4 times more varus-valgus and up to 7 times more A-P angulation. The technique developed for measuring the three-dimensional motion of fractures may have wide applications in further biomechanical and fracture healing studies.

Biomechanical Phenomena↗
PubMed1991

NGF gene expression in actively growing brain glia.

Previous work suggested that brain NGF acts locally on cells adjacent to sites of synthesis, in addition to any putative actions on distant, projecting perikarya. To define the basis of local action, we used a sensitive nuclease protection assay to identify cells expressing the NGF gene in vivo and in vitro. In addition to neurons, glia from a variety of developing brain areas synthesized NGF mRNA, suggesting that CNS glia exhibit a generalized capacity to express the gene. Expression was associated with active glial growth. Stimulation of growth with serum increased NGF message 2-fold in culture. Moreover, rapidly growing, low-density glial cultures exhibited 8-fold higher levels of NGF mRNA than quiescent, confluent cultures. The optic nerve, which contains all 3 major types of glia, expressed the message in vivo during neonatal development. In contrast, expression was barely detectable in the adult optic nerve. Transection, which induces glial proliferation, elicited de novo appearance of NGF mRNA in the adult nerve. Our observations suggest that active glial growth is associated with expression of the NGF gene and raise the possibility that actively growing glia in the developing or injured brain regulate neuronal growth through the elaboration of NGF.

Animals↗
PubMed1990

Comparison of right ventricular impedance, pulse pressure and maximal dP/dt for determination of hemodynamic stability of ventricular arrhythmias associated with coronary artery disease.

By monitoring hemodynamic parameters, a future generation of automatic implantable defibrillators will provide tiered therapy of ventricular arrhythmias according to the associated hemodynamic compromise. Changes in intracardiac impedance permit beat-to-beat assessment of ventricular volumes and make this parameter attractive as a rapid discriminator of hemodynamic compromise during arrhythmias. Beat-to-beat changes in right ventricular (RV) impedance were measured before, during and after 27 episodes of ventricular tachyarrhythmias induced in 17 men (64 +/- 7 years, mean +/- standard deviation; left ventricular ejection fraction 41 +/- 11%). Impedance was measured using a tripolar lead system and was compared to ventricular tachycardia cycle length, RV pulse pressure and maximum systolic RV dP/dt as indicators of systemic hemodynamic compromise. The average decreases in systolic blood pressure and mean arterial pressure during ventricular tachycardia were 48 +/- 23% and 46 +/- 26%, respectively (mean +/- standard deviation; p less than 0.001 for each). Right ventricular impedance decreased an average 39 +/- 22% from its baseline value (p less than 0.001) during ventricular tachycardia. The percent change in impedance from baseline during ventricular tachycardia correlated significantly with the percent decrease in systolic and mean arterial pressure (r = 0.45 and 0.42, respectively; both p less than 0.05). Right ventricular dP/dt correlated the most poorly of all parameters with changes in blood pressure while impedance X RV pulse pressure correlated best with changes in mean and systolic pressure (r greater than or equal to 0.82, p less than 0.001).

Aged↗
PubMed1990

Usefulness of right ventricular pulse pressure as a potential sensor for hemodynamically unstable ventricular tachycardia.

The automatic implantable cardioverter defibrillator has had a major impact on the management of patients with ventricular tachyarrhythmias. Future devices will offer tiered therapy for ventricular arrhythmias, based on a sensor capable of discriminating hemodynamically stable from unstable ventricular tachycardia (VT). We studied 27 patients with sustained VT/ventricular fibrillation during 70 episodes of sustained ventricular arrhythmias (greater than 30 seconds or requiring cardioversion). In this study, phasic arterial pressure (mm Hg), VT cycle length (ms) and right ventricular (RV) pulse pressure (mm Hg) were measured before, during the first 30 beats and after each episode of VT. During the first 10 beats of 23 episodes of unstable VT, the mean (+/- standard error of the mean) decrease in RV pulse pressure from baseline was 22 +/- 1.8 mm Hg; it was 13.8 +/- 2.4 mm Hg during the first 10 beats of 47 episodes of stable VT, (p = 0.01, stable vs unstable). For the next 20 beats of VT, RV pulse pressure decreased from baseline by 22 +/- 2.5 mm Hg during unstable and by 12.0 +/- 2.5 mm Hg during stable VT (p = 0.0001, stable vs unstable). The percent decrease of RV pulse pressure correlated well with the percent decrease in mean arterial pressure and percent decrease in systolic arterial pressure (r = 0.70; r = 0.69, respectively; p less than 0.001) during VT, but poorly with the VT cycle length (r = 0.27, p less than 0.05). The percent decrease in RV pulse pressure is a useful hemodynamic sensor for discriminating between stable and unstable VT.

Arrhythmias, Cardiac↗
PubMed1990

A prospective study of right ventricular pulse pressure and dP/dt to discriminant-induced ventricular tachycardia from supraventricular and sinus tachycardia in man.

In the future, automatic implantable cardioverter defibrillators (AICD) may incorporate sensors to differentiate hemodynamically stable from unstable ventricular tachycardias (VT). These sensors should also discriminate between ventricular and supraventricular tachycardias to avoid inappropriate responses from the device. Right ventricular pulse pressure (RVPP) and maximal systolic right ventricular dP/dt (dP/dt) were measured before, during and after 91 episodes of hemodynamically stable VT (VTs), hemodynamically unstable VT (VTus), supraventricular tachycardia (SVT) and sinus tachycardia (ST) induced in 49 male patients. The mean percent changes (mean +/- S.E.M.) in RVPP from baseline (% delta RVPP) during VTs and VTus were -35 +/- 3% and -72 +/- 3%, respectively (both P less than 0.001). The % delta RVPP during ST was +56 +/- 11% (P less than 0.01) and % delta RVPP was unchanged from baseline during SVT (+2 +/- 9%; P greater than 0.01). Mean % change in RV dP/dt from baseline was -20 +/- 3% during VTs (P less than 0.001), -36 +/- 5% during VTus (P less than 0.001), +15 +/- 13% during SVT (P less than 0.01), and +85 +/- 23% during ST (P greater than 0.01). The mean percent changes in RVPP were significantly different between each arrhythmia group (P less than 0.01). The mean % changes in RV dP/dt were significantly different only between ST and VTs or VTus and between SVT and VTus. The range of values for % delta RVPP during VTs overlapped considerably with the ranges of % delta RVPP during VTus and SVT. The ranges of % delta RVPP overlapped minimally between VTus and SVT. Percent change RVPP separated each episode of VTs and VTus from those of ST. The range of common values for % delta dP/dt between all four groups was extensive. It is concluded that % delta RVPP from baseline is significantly different between groups of patients during VTs, VTus, SVT, and ST, but that a large degree of overlap in the range of values for % delta RVPP and RV dP/dt between different arrhythmias groups may limit the specificity of these hemodynamic variables in separating different arrhythmias.

Cardiac Pacing, Artificial↗
PubMed1990

[Direct injection of plasma to determine famotidine in plasma using HPLC column switching technique].

An automated high performance liquid chromatographic switching system is described for the analysis of famotidine, an H2-receptor antagonist in plasma. The system used YWG-C18 short precolumn for on-line sample clean-up and a Shimpack CLC-ODS analytical column for separation. A solution of 0.2 mol/L acetic acid was used as pretreatment mobile phase and 14% (v/v) methanol in ammonium acetate (0.2 mol/L) was used as analytical mobile phase. The detection was at 267 nm and the detection limit was 12 ng/ml plasma. Plasma sample was diluted with acetic acid (0.2 mol/L) and injected directly on the HPLC system. The procedure of clean-up is simple and automatic. The recovery of clean-up is 84.1%.

Adult↗
PubMed1990

Correlation of an invasive measure of right ventricular pressure and mean arterial pressure.

Recently, cardiac pacemakers have been introduced which increase heart rate during exercise. Current rate responsive pacemakers achieve this objective by monitoring minute ventilation via a transvenous impedance measurement and provides a proportional heart rate increase with increases in minute ventilation. These devices are independent of hemodynamic parameters. Therefore, the potential exists for a sufficiently high rate which results in decreased cardiac output by virtue of Starling's Principle. An invasive measure of right ventricular (RV) pressure is compatible with the power and complexity of contemporary implantable pacemakers. In addition, mean arterial pressure is accepted as a diagnostic indicator of left ventricular hemodynamic compromise. Therefore, a correlation of right ventricular pressure and mean arterial pressure was undertaken. Twenty-six patients were studied during normal sinus rhythm and ventricular tachycardia during routine electrophysiology examination. A beat to beat measure of peak to peak RV pressure resulted in a correlation coefficient of 0.68 with mean arterial pressure.

Blood Pressure↗
PubMed1989

Expression of NGF and NGF receptor mRNAs in the developing brain: evidence for local delivery and action of NGF.

Nerve growth factor (NGF) is a well-documented target-derived trophic factor in the peripheral nervous system. Recently, proteins as well as mRNAs for both NGF and its receptor (NGF-R) have been detected in diverse areas in the central nervous system (CNS). Considerable evidence suggests that NGF also functions in the target synthesis/retrograde transport mode in the brain. For example, NGF is synthesized in the target hippocampus, as indicated by the presence of NGF message, and interacts with the receptors on terminals projecting from basal forebrain, where receptor mRNA is detectable. Spatial separation of NGF and receptor gene expression is consistent with the target mechanism of action. To ascertain whether local action may also occur in the CNS, we used sensitive nuclease protection assays to study the relationship of NGF and NGF-R expression in the developing brain. Our results indicate that in some brain areas, such as diencephalon, postnatal hippocampus, and olfactory bulb, NGF message was highly expressed, while receptor mRNA was virtually undetectable, suggesting that these areas serve as target sources of NGF for distant afferent neurons. By contrast, in other brain areas, such as cerebellum, striatum, perinatal olfactory bulb, and prenatal hippocampus, NGF and NGF-R mRNAs were coexpressed and coregulated developmentally. Consequently, local delivery and action of the trophic molecule may occur in these areas during these periods. We tentatively conclude that NGF may act through both distant and local modes in the developing CNS.

Animals↗