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At least 793 records · Page 44Linked to original sources
PubMed2000

DRacGAP, a novel Drosophila gene, inhibits EGFR/Ras signalling in the developing imaginal wing disc.

We have identified a novel Drosophila gene, DRacGAP, which behaves as a negative regulator of &Rgr;-family GTPases DRac1 and DCdc42. Reduced function of DRacGAP or increased expression of DRac1 in the wing imaginal disc cause similar effects on vein and sensory organ development and cell proliferation. These effects result from enhanced activity of the EGFR/Ras signalling pathway. We find that in the wing disc, DRac1 enhances EGFR/Ras-dependent activation of MAP Kinase in the prospective veins. Interestingly, DRacGAP expression is negatively regulated by the EGFR/Ras pathway in these regions. During vein formation, local DRacGAP repression would ensure maximal activity of Rac and, in turn, of Ras pathways in vein territories. Additionally, maximal expression of DRacGAP at the vein/intervein boundaries would help to refine the width of the veins. Hence, control of DRacGAP expression by the EGFR/Ras pathway is a previously undescribed feedback mechanism modulating the intensity and/or duration of its signalling during Drosophila development.

Amino Acid Sequence↗
PubMed2002

Enhanced method for the reconstruction of zero-dispersion wavelength maps of optical fibers by measurement of continuous-wave four-wave mixing efficiency.

The zero-dispersion wavelength map of an optical fiber can be obtained from measurement of end-to-end four-wave mixing efficiency at various wavelengths. A fast and unambiguous algorithm for reconstruction of the zero-dispersion wavelength map of an optical fiber by measurement of four-wave mixing efficiency is proposed. This method can produce high-resolution results in a few seconds. We also study the limitations of this technique that are due to polarization-mode dispersion (PMD). Simple practical rules to avoid the effects of PMD in such measurements are established.

Journal Article↗
PubMed2000

The effect of baroreflex adaptation on the dynamic cardiovascular response to head-up tilt.

BACKGROUND: Baroreflex adaptation to repetitive +Gz has been reported previously. The underlying mechanism may involve different responses of stroke volume (SV) and total peripheral resistance (TPR) to +Gz. HYPOTHESIS: The previously observed enhanced mean arterial pressure (MAP) regulation in fighter pilots (FP) is mediated by increases in SV and/or TPR. METHODS: There were 8 pilots and 12 non-pilots who underwent head-up tilt. SV was determined using impedance cardiography. RESULTS: MAP increased significantly in FP, due to heart rate (HR) and TPR increasing more and SV decreasing less. CONCLUSION: Baroreflex adaptation results in better performance of HR, SV and TPR in response to +Gz.

Adaptation, Physiological↗
PubMed2001

Cardiovascular effects of verapamil and quinidine at normal and elevated ambient pressure.

Cardiovascular parameters were measured in rats before and after administration of verapamil and quinidine, a slow Ca2+ and fast Na+ channel blocker, respectively, at normal and elevated ambient pressure [5 bar (500 kPa)]. Left ventricular pressure (Pivt), maximal velocity of Plvt rise (+dP/dt) and fall (-dP/dt), and heart rate (HR), arterial systolic pressure (Pasys), and mean arterial pressure (MAP) were measured in all animals using catheters connected to pressure transducers. Cardiac output (Q), and myocardial blood flow (MBF) were detected by the microsphere technique. Total peripheral vascular resistance (TPVR), myocardial vascular resistance (MVR) and oxygen consumption of the heart (VO2) was calculated. In Groups 1a (control group; 1 bar) and 1b (test group; 1-5 bar), verapamil (1.5 mg x kg(-1)) caused a reduction in Plvt, +dP/dt, -dP/dt, Pasys, MAP, VO2, TPVR, and MVR in both groups at 1 bar (100 kPa), and these parameters remained depressed for at least 50 min in Group 1a. However, MBF increased after verapamil injection. After compression to 5 bar (500 kPa), Plvt, dP/dt, Pasys, VO2, and MBF were markedly elevated (Group 1b). No change in HR, SV, or Q was found in either of the groups. In Groups 2a (control group; 1 bar) and 2b (test group; 1-5 bar), quinidine (5 mg x kg(-1)), infused over a period of 10 min, reduced Plvt, +dP/dt, -dP/dt, MAP, Pasys, VO2, Q, stroke volume (SV), TPVR and MBF at 1 bar (100 kPa). These parameters remained depressed for almost the whole experimental period in Group 2a, while Plvt, +/-dP/dt, Pasys, MAP and VO2 were enhanced during exposure to 5 bar (500 kPa) in Group 2b. The HR was unchanged by quinidine in Group 2a, but was increased at elevated ambient pressure in Group 2b, whereas the MBF was unchanged in both groups. The present results show that verapamil and quinidine have a depressant effect on cardiac function, arterial pressure and VO2 at normal atmospheric pressure, whereas MBF was enhanced only in the verapamil group. During exposure to elevated ambient pressure, cardiac function, arterial pressure and VO2 increased despite adequate inhibition of slow Ca2+ and fast Na+ channels.

Air Pressure↗
PubMed2003

Watching symptoms and illnesses through the eyes of Multiple Correspondence Analysis: a case study in toxicology.

The goal of the reported research was the design of a computerized tool aimed at aiding an emergency specialist, in a toxicological emergency unit, to quickly identify, at the admission time, the various poisons ingested by a comatose patient. This medical decision making problem has been proved to be computationally intractable since a lot of patient cases sharing the same clinical table have different diagnoses in terms of psychotropes combinations. The paper explores the idea that the outcome of Multiple Correspondence Analysis (MCA), a mathematical data analysis method, can be thought of as visual and analytical aids for the physician facing this decision problem. We argue that the expert's clinical reasoning can be enhanced by the factorial maps and some computerized results provided by MCA. Using a learning database of 505 diagnosed cases, we realized a whole decision aiding system called TOXSYMEDIA. A test-base of 97 patients was used to partially assess the system. The method and resulting tool revealed to be appreciable to early inform the physician about the possible combination of ingested psychotropes.

Coma↗
PubMed2004

[MRI representations of glioma radioencephalopathy].

BACKGROUND & OBJECTIVE: Correctly distinguishing normal tissue reactive changes, tumor residue or relapse, and radioencephalopathy of glioma after radiotherapy by imaging methods is difficult. This study was to analysis MRI representations of glioma radioencephalopathy. METHODS: MRI records of 5 patients with golima radioencephalopathy treated in our hospital from Sept. 1998 to May 2004 were collected, 4 cases were confirmed by operation, and 1 was diagnosed by MRI and PET. All these 5 cases were suspected recurrence in MRI scans after 1 or 2 radiotherapy periods, but them were confirmed radioencephalopathy pathologically after excision. RESULTS: MRI revealed all patients deteriorated within 40 days to 7 months. The edema aggravated (5/5), and most were moderate or severe (4/5). Space occupying signs aggravated (5/5). Lesions enlarged (5/5) with irregular shapes like coral, map, or ring in enhanced scans. CONCLUSIONS: Radioencephalopathy of glioma occurs within 2 years after radiotherapy mostly. MRI scans manifest edema and space occupying signs aggravated, meanwhile the lesions enlarged progressively in a rather short time. It is characteristic that enhanced lesions were irregular and radiate.

Adolescent↗
PubMed1991

The morphology and function of echocardiography.

Ultrasonographic methods rely on piezoelectric effects that define the reflection of sound energy from either moving blood or tissue. Noninvasive imaging of cardiac structures has altered the practice of cardiology over the past decade. During recent years, Doppler echocardiography has brought important advances in the assessment of cardiac morphology and function. Doppler color flow mapping studies have greatly enhanced both structural and functional assessment and the evaluation of congenital and acquired cardiac diseases. Although two-dimensional echocardiography is an established tool in clinical cardiology, the image quality of conventional transthoracic approaches can sometimes be unsatisfactory for various reasons. In such cases, transesophageal echocardiography can provide important diagnostic information. Furthermore, some structures that are poorly visualized on standard precordial echocardiography can be observed better on the transesophageal approach.

Echocardiography↗
PubMed1988

Combined H1 and H2 receptor blockade attenuates the cardiovascular effects of high-dose atracurium for rapid sequence endotracheal intubation.

Large doses of atracurium (1.5 mg/kg) (six times the ED95) can result in significant histamine release, resulting in systemic hypotension. The efficacy of histamine receptor blockade in attenuating atracurium induced hypotension was therefore studied. Four groups of seven patients each were studied: group I, control; group II, H1 blockade (1 mg/kg diphenhydramine); group III, H2 blockade (cimetidine 4 mg/kg); and group IV, H1 and H2 blockade (diphenhydramine 1 mg/kg and cimetidine 4 mg/kg). All patients were anesthetized with an intravenous narcotic-nitrous oxide technique and then given 1.5 mg/kg atracurium. In group I, mean arterial pressure (MAP) decreased 30 mm Hg after 2 minutes and remained 25 mm Hg below baseline at 3 minutes, a change significantly greater than that in group IV, in which MAP decreased 8 and 7 mm Hg, respectively. H1 receptor blockade was associated with no significant attenuation of changes in MAP. H2 receptor blockade alone was associated with significant decreases in MAP, possibly secondary to enhanced release of histamine via an antagonist effect on recently described H3 receptors. Plasma histamine levels increased significantly 2 minutes after atracurium administration and correlated with hemodynamic changes. It is concluded that combined H1 and H2 receptor blockade attenuates cardiovascular effects associated with large doses of atracurium in humans. Histamine-releasing agents may be contraindicated in patients subject to chronic H2 receptor blockade.

Atracurium↗
PubMed1995

Megakaryocyte-specific positive regulatory sequence 5' to the human PF4 gene.

Platelet factor 4 (PF4) is only expressed in platelets and is an appropriate marker for studying megakaryocytic differentiation. We previously characterized cDNA and genomic clones for human PF4 (hPF4) and now present transient expression studies defining the promoter of the gene. 12-O-tetradecanoyl-phorbol-13- acetate (TPA) induces megakaryocytic differentiation of human erythroleukemia (HEL) cells, providing an excellent model system for the study of megakaryocyte-specific promoter activity. Luciferase reporter-gene constructs containing sequences from -2074 to +49 were used to map regions that may regulate PF4 gene expression. The sequence in the region -239 to -107 increased basal promoter activity by four- to five-fold in TPA-induced HEL cells. The sequence between -239 and -107 contains 53 consecutive thymidine residues. Functional studies using constructs in this region show that poly(T) and the region -187 to -107 are necessary for the total increase in activity in TPA-induced HEL cells. Mobility-shift assays show that the poly(T) tract binds TPA-inducible proteins. The results suggest a complex promoter for the PF4 gene involving a basal nonspecific promoter element between -107 and +49, a positive promoter element between -239 and -107 binding specific nuclear proteins from megakaryocyte-lineage cells, and a silencer-like region between -2074 and -1653.

Base Sequence↗
PubMed1994

Tyrosines1234-1235 are critical for activation of the tyrosine kinase encoded by the MET proto-oncogene (HGF receptor).

The tyrosine kinase encoded by the MET proto-oncogene (p190MET) is the receptor for Hepatocyte Growth Factor/Scatter Factor (HGF/SF). Previous work has shown that autophosphorylation of p190MET enhances its enzymatic activity and that the major phosphorylation site is Tyr1235, located in the catalytic domain. This residue is part of a 'three tyrosine' motif, including Tyr1230, Tyr1234, and Tyr1235, conserved in several other receptor kinases. We studied the role of these tyrosines in the positive regulation of the p190MET kinase by site-directed mutagenesis. Substitution of either Tyr1235 or Tyr1234 with phenylalanine severely reduced the in vitro kinase activity toward exogenous substrates. Kinetic experiments showed that the residual activity of these mutants could still be enhanced by autophosphorylation. Phosphopeptide mapping indicated that, in the absence of Tyr1235, Tyr1234 is phosphorylated. Only the replacement of both Tyr1234 and Tyr1235 yielded a mutant which completely lost the ability to be activated by autophosphorylation. In stable transfectants expressing the HGF/SF receptor with single substitution of either Tyr1234 or Tyr1235 the response to HGF/SF was impaired. The ligand did not induce tyrosine phosphorylation of the receptor nor stimulated chemotaxis. These data show that Tyr1234 and Tyr1235 are critical for the activation of the HGF/SF receptor kinase both in vitro and in response to the ligand in intact cells.

3T3 Cells↗
PubMed2000

Enhanced intake of high-fat food following striatal mu-opioid stimulation: microinjection mapping and fos expression.

Our previous studies have shown that stimulation of mu-opioid receptors within the nucleus accumbens preferentially enhances intake of palatable food containing sucrose and fat; thus, opioids in this brain area may mediate the rewarding characteristics of food by modulating taste and macronutrient preference. The present study was designed to further explore the nature of the involvement of striatal opioids in feeding behavior, such as the location of sensitive subregions of the ventral striatum and the brain neural circuits involved in opioid-mediated hyperphagia. In Experiment 1, we conducted a microinfusion mapping study of feeding behavior by microinfusion of the mu receptor agonist, D-Ala(2),NMe-Phe(4), Glyol(5)-enkephalin (0, 0.025 and 0.25 microg/0.5 microl per side; equivalent to 0, 0.04 and 0.40 nmol/0.5 microl per side), into several striatal subregions. In Experiment 2, detection of the expression of the immediate early gene, c-fos, was used to examine brain areas activated following intra-striatal microinfusion of D-Ala(2), NMe-Phe(4),Glyol(5)-enkephalin. The microinjection mapping study demonstrated a broad anatomical gradient within the striatum, with sensitivity highest in relatively more lateral and ventral regions of the striatum (ventrolateral striatum, lateral shell and core). The Fos mapping study demonstrated that circuitry including hypothalamic areas, the ventral tegmental area, the substantia nigra and the nucleus of the solitary tract was recruited by stimulation of mu receptors within the nucleus accumbens. A similar pattern was observed following stimulation of mu receptors in the dorsal striatum; however, the extent of activation was much smaller in magnitude. These results suggest that the role of mu receptors within the striatum in palatable feeding primarily involves ventral and lateral regions. Moreover, the pattern of activation in hypothalamic, midbrain and gustatory-visceral relay areas suggests that striatal mu receptors may participate in integrating motivational, metabolic and autonomic aspects of ingestive behavior.

Analgesics, Opioid↗
PubMed2000

Ultrasound perfusion imaging of the human brain.

BACKGROUND AND PURPOSE: Color-coded perfusion maps can be calculated from ultrasound harmonic gray-scale imaging data to analyze brain tissue perfusion. METHODS: In 13 healthy volunteers, 2 doses (0.5 and 1.5 mL) of Optison, a perfluoropropane-containing ultrasound contrast agent, were injected intravenously, and they produced a strong increase in echo enhancement in the brain parenchyma. The contrast agent was injected twice for ultrasound examination of both hemispheres. A total of 24 hemispheres per dose was available for further analysis. We used harmonic imaging for quantification of echo enhancement. Color-coded perfusion maps were calculated from the ultrasound data. In 1 subject, magnetic resonance images were obtained parallel to the orientation of the ultrasound scans. RESULTS: After administration of both doses of Optison, it was possible to evaluate brain tissue perfusion in all 24 hemispheres. Subtraction of precontrast images and color coding enhanced the visualization of hemispheric perfusion. The epiphyseal gland, anterior interhemispheric fissure, third ventricle, and lateral fissure can be used as reliable anatomic landmarks. Artifacts caused by abrupt changes in thickness of the temporal bone are observed as signal-void streaks oriented from the ultrasound probe toward the cerebral midline. CONCLUSIONS: Harmonic gray-scale imaging with Optison shows strong echo enhancement in the brain parenchyma. By calculating color-coded perfusion maps, it is possible to visualize human brain tissue perfusion at the patient's bedside.

Adult↗
PubMed1998

Measurement of tumor vascular volume and mean microvascular random flow velocity magnitude by dynamic Gd-DTPA-albumin enhanced and diffusion-weighted MRI.

Tumor vascular volume fraction and the magnitude of the mean microvascular random flow velocity were measured in an animal tumor model by combining dynamic Gd-DTPA-albumin enhanced MRI and diffusion-weighted MRI in conjunction with a compartmental modeling analysis. The vascular volume fraction maps were obtained from the dynamic Gd-DTPA-albumin enhanced MRI measurement. It was found that the vascular volume fraction for Walker 256 tumor was higher within the outgrowing rim and decreased towards the central region. The average value obtained from five animals was 0.062 +/- 0.009 ml/g. By using the vascular volume fraction from the Gd-DTPA-albumin enhanced MRI measurement, maps of the magnitude of the mean microvascular random flow velocity were obtained from the diffusion-weighted MRI measurements with the compartmental modeling analysis. The relative extravascular and intravascular contributions to the diffusion-weighted MRI signal were determined for three tissue groups with different Gd-DTPA-albumin enhancement characteristics, and the flow and molecular diffusion-induced attenuation factors for the intravascular compartment were also compared. The mean microvascular random flow velocity magnitude maps were obtained with an average value of 0.67 +/- 0.06 mm/s.

Albumins↗
PubMed1990

Microtubule-associated proteins from Antarctic fishes.

Microtubules and presumptive microtubule-associated proteins (MAPs) were isolated from the brain tissues of four Antarctic fishes (Notothenia gibberifrons, N. coriiceps neglecta, Chaenocephalus aceratus, and a Chionodraco sp.) by means of a taxol-dependent, microtubule-affinity procedure (cf. Vallee: Journal of Cell Biology 92:435-442, 1982). MAPs from these fishes were similar to each other in electrophoretic pattern. Prominent in each preparation were proteins in the molecular weight ranges 410,000-430,000, 220,000-280,000, 140,000-155,000, 85,000-95,000, 40,000-45,000, and 32,000-34,000. The surfaces of MAP-rich microtubules were decorated by numerous filamentous projections. Exposure to elevated ionic strength released the MAPs from the microtubules and also removed the filamentous projections. Addition of fish MAPs to subcritical concentrations of fish tubulins at 0-5 degrees C induced the assembly of microtubules. Both the rate and the extent of this assembly increased with increasing concentrations of the MAPs. Sedimentation revealed that approximately six proteins, with apparent molecular weights between 60,000 and 300,000, became incorporated into the microtubule polymer. Bovine MAPs promoted microtubule formation by fish tubulin at 2-5 degrees C, and proteins corresponding to MAPs 1 and 2 co-sedimented with the polymer. MAPs from C. aceratus also enhanced the polymerization of bovine tubulin at 33 degrees C, but the microtubules depolymerized at 0 degrees C. We conclude that MAPs are part of the microtubules of Antarctic fishes, that these proteins promote microtubule assembly in much the same way as mammalian MAPs, and that they do not possess special capacities to promote microtubule assembly at low temperatures or to prevent cold-induced microtubule depolymerization.

Alkaloids↗
PubMed1999

Role of tissue angiotensin II in myocardial remodelling induced by mechanical stress.

In an in vivo study, spontaneously hypertensive rats (SHR) were treated with an angiotensin II (Ang II) type 1 receptor antagonist of candesartan or hydralazine. Untreated SHR progressively developed severe hypertension, and treatment with candesartan or hydralazine decreased blood pressure. Candesartan reduced left ventricular (LV) weight, LV wall thickness, transverse myocyte diameter, the relative amount of V3 myosin heavy chain, and interstitial fibrosis, while treatment with hydralazine slightly prevented an increase in LV wall thickness, but did not exert a significant reduction on other parameters. In an in vitro study, neonatal rat cardiomyocytes were cultured on deformable silicone dishes. Stretching cardiomyocytes activated second messengers such as protein kinase C, Raf-1 kinase, and mitogen-activated protein (MAP) kinase, increasing protein synthesis, enhancing endothelin (ET)-1 release, activating the Na+/H+ ion exchanger. Moreover, pretreatment with candesartan diminished an increase in phenylalanine incorporation, MAP kinase activity, and c-fos gene expression induced by the stretching of cardiomyocytes. This suggests that the cardiac renin-angiotensin system is linked to the formation of pressure-overload hypertrophy and that Ang II increases the growth of cardiomyocytes by an autocrine mechanism. Finally, we examined the signalling pathways leading to MAP kinase activation both in cardiac myocytes and in cardiac fibroblasts. Ang II-evoked signal transduction pathways differed between cell types. In cardiac fibroblasts, Ang II activated MAP kinase through a pathway including the Gbetagamma subunit of Gi protein, Src, Shc, Grb2, and Ras, while Gq and protein kinase C were important in cardiac myocytes.

Angiotensin II↗
PubMed2006

Velocity map imaging study of BrCl photodissociation at 467 nm: determination of all odd-rank (K = 1 and 3) anisotropy parameters for the Cl(2P(3/2)0) photofragments.

Resonance-enhanced multiphoton ionization and velocity map imaging of the Cl(2P(3/2)0) fragments of BrCl photolysis at 467.16 nm have been used to obtain a complete set of orientation parameters (with ranks K = 1 and 3) describing the polarization of the electronic angular momentum. The experiments employ two geometries distinguished only by the circular or linear polarization of the photolysis laser beam. Normalized difference images constructed from the data accumulated using a right or left circularly polarized probe-laser beam, counterpropagating with the photolysis laser, were fitted to basis images corresponding to contributions from various odd-rank anisotropy parameters. Expressions are given for the difference images in terms of the K = 1 and 3 anisotropy parameters, which describe coherent and incoherent parallel and perpendicular excitation and dissociation mechanisms. The nonzero values of the anisotropy parameters are indicative of nonadiabatic dissociation dynamics, with likely contributions from flux on the A 3Pi1,B 3Pi(0+),C 1Pi1, and X 1sigma+(0+) states as well as one further omega = 1 state, all of which correlate adiabatically to Cl(2P(3/2)0) + Br(2P(3/2)0) photofragments. The magnitudes of the parameters depend both on the amplitudes of dissociative flux in these states, and also on the phases accumulated by the nuclear wave functions for different dissociation pathways.

Journal Article↗
PubMed1993

Immunogenicity of multiple antigen peptides containing B and non-repeat T cell epitopes of the circumsporozoite protein of Plasmodium falciparum.

We have characterized the immune response of mice to multiple Ag peptide systems (MAP) containing the immunodominant B cell epitope (NANP)3 and one of three distinct Th epitopes, Th2R, Th3R, and CS.T3, of the C terminal region of the circumsporozoite protein of Plasmodium falciparum, a human malaria parasite. Mice of three different MHC haplotypes (H-2k, H-2d, and H-2a) were immunized with the various MAP constructs. Mice of all three strains produced antibodies, but their anti-sporozoite titers were considerably lower than their anti-peptide titers as detected by ELISA. These antibodies reacted at high titers not only with the repeat polymer (NANP)50, but also with MAP that contained only the respective Th sequence. The antibody binding site within each of the Th sequences was mapped, using truncated peptides, in an inhibition assay. A primary antibody response, induced by a single i.v. inoculation of sporozoites, was greatly enhanced by the injection of MAP.

Amino Acid Sequence↗