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At least 703 records · Page 39Linked to original sources
PubMed2006

Responses of excitatory hippocampal synapses to natural stimulus patterns reveal a decrease in short-term facilitation and increase in short-term depression during postnatal development.

Schaffer collateral excitatory synapses onto CA1 pyramidal cells are subject to significant modulation by short-term plasticity. This presynaptic, history-dependent modulation of neurotransmitter release causes synaptic transmission to be sensitive to the frequency of the input. As a result, temporally irregular input patterns, such as those observed in vivo, produce synaptic responses over a very wide dynamic range that reflect a balance of short-term facilitation and short-term depression. The neonatal period is an important developmental period in the hippocampus, when functional representations of an animal's environment are being established through exploratory behavior. The strength of excitatory synapses and their modulation by short-term plasticity are critical to this process. One form of short-term plasticity, paired-pulse facilitation, has been shown to decrease as juvenile rats mature into young adults. However, little is known about the neonatal modulation of other forms of short-term plasticity, including the responses to temporally complex stimuli. We examined developmental modulation of the short-term dynamics of Schaffer collateral excitatory synapses onto CA1 pyramidal cells in acute hippocampal slices, using both constant frequency stimuli and natural stimulus patterns that were taken from in vivo recording of spike patterns of hippocampal cells. In response to constant frequency stimulation, synapses in slices from young adult rats (P28-P35) showed less short-term depression than did those in slices from juveniles (P12-P18). However, when the natural stimulus pattern (containing a wide mix of frequencies) was used, synapses from young adults instead showed more short-term depression and less short-term facilitation than did juveniles. Comparing the natural stimulus pattern responses with constant frequency stimulation of a similar frequency, we found that the average responses were similar in young adults (both showed modest depression). However, in juveniles, the natural pattern produced robust facilitation while constant frequency stimulation caused a large short-term depression. Our results reveal that there are developmental changes both in individual forms of short-term plasticity and in the relative balance between short-term facilitation and short-term depression that will alter the signal transfer characteristics of these synapses.

Animals↗
PubMed1998

[Low-dose dobutamine echocardiographic assessment of reversible contractile dysfunction (myocardial stunning) after myocardial infarction].

Low dose (5 to 10 micrograms/min) dobutamine echocardiography was used to predict the presence of reversible contractile dysfunction (myocardial stunning) after myocardial infarction successfully revascularised in the acute phase of primary angioplasty. The investigation was undertaken in 40 patients, 4 +/- 1 days after inaugural myocardial infarction. The left ventricle was divided into 16 segments. Viable myocardium was diagnosed when the initial regional wall motion score decreased by at least 2. Resting echocardiography was performed at 2 months to evaluate the effective recovery of regional wall motion (myocardial viability). The presence of contractile reserve was documented by dobutamine echocardiography in 18 patients (45%). The sensitivity, specificity and positive and negative predictive values of dobutamine echocardiography for the diagnosis of myocardial viability were 82, 83, 78 and 86% respectively. The negative predictive value was high in all dysnergic segments (86%). The positive predictive value of the investigation was however higher in hypokinetic than in akinetic segments (73 vs 21%; p < 0.05). The recovery of regional wall motion during follow-up was statistically related to higher initial left ventricular ejection fraction (p < 0.04), the presence of angiographically documented collateral circulation before revascularisation (p = 0.007), the contractile response to dobutamine (p = 0.0001) and was observed more frequently in hypokinetic than in akinetic segments (p < 0.05). These results show that low-dose dobutamine echocardiography is a sensitive and specific investigation for predicting irreversible myocardial damage after successful primary angioplasty in acute myocardial infarction. However, even in the absence of residual coronary stenosis, the presence of viable myocardium is only identified specifically in hypokinetic segments.

Aged↗
PubMed1999

Clinical application of perfusion and diffusion MR imaging in acute ischemic stroke.

With the advances in new neuroimaging modalities, the role of imaging of acute ischemic stroke has broadened and progressed from making diagnoses to providing valuable information for patient management. The goal of thrombolytic therapy for acute ischemic stroke should be to salvage the ischemic tissue reversibility that can respond to recanalization and avoid reperfusion of the dead (nonviable) tissue. It is essential to have rapid diagnostic modalities that can distinguish viable ischemic tissue from irreversibly damaged tissue, because there is a risk of reperfusion injury such as hemorrhagic complications with early intervention. Although diffusion magnetic resonance (MR) imaging has been reported to have a high sensitivity and specificity for acute ischemia in acute stroke patients without early reperfusion therapy, the capability to differentiate reversible from irreversible ischemia by diffusion MR imaging has not been established. Perfusion MR imaging techniques provide direct information on parenchymal perfusion status (adequacy of the collateral circulation) and may have the potential for providing important information about tissue viability and/or reversibility for selecting appropriate patients for thrombolytic therapy.

Animals↗
PubMed1989

Differential vasoreactivity to the thromboxane A2 mimic U-46619 of collateral and normal peripheral blood vessels in situ perfused rat hindquarters.

In situ perfusion of rat hindquarters was performed through both iliac arteries. Perfusion pressures were measured concomitantly in the normal vascular bed and in the ligation-induced collateral bed of the left and right hindleg, respectively. An increased vaso-constrictive response of the collateral versus normal blood vessels was found after bolus injections of increasing concentrations of the thromboxane A2 (TXA2) mimic U-46619. This increased reactivity was related to a difference in vascular structure and in receptor-mediated sensitivity. The vasoconstrictive effect of U-46619 was dose-dependently inhibited by the combined TXA2 synthetase inhibitor-TXA2/prostaglandin endoperoxide (PGH2) receptor antagonist ridogrel and the single TXA2/PGH2 receptor antagonist sulotroban. Selective blockade of alpha 1-, alpha 2-, beta 1-beta 2- and S2-receptors, cyclooxygenase inhibition, TXA2 synthesis inhibition, amine depletion and amine uptake blockade had no influence on the vasoconstrictive action of U-46619. Ca2+ entry blockade by flunarizine and nifedipine significantly reduced the vasoconstriction. This study shows that (1) rat peripheral collaterals in relation to normal arterial blood vessels are significantly more reactive to TXA2; (2) the vasoconstrictive effect of U-46619 is mediated predominantly by TXA2/PGH2 receptors; (3) the activation of these receptors elicits indirectly transmembrane Ca2+ entry to trigger vasoconstriction.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2005

Nerve growth factor-mediated collateral sprouting of central sensory axons into deafferentated regions of the dorsal horn is enhanced in the absence of the p75 neurotrophin receptor.

This study examined the growth capacity of nerve growth factor (NGF)-responsive dorsal root ganglion (DRG) central processes using mice of the following genotypes: wildtype, p75 neurotrophin receptor (p75NTR) exon III null mutant, NGF transgenic, and NGF transgenic with p75NTR exon III null mutation (NGF/p75(-/-)). In wildtype and p75NTR exon III null mutant mice calcitonin gene-related peptide (CGRP) immunoreactivity in the dorsal horn is dramatically reduced at both 3 and 28 days after rhizotomy. NGF transgenic and NGF/p75(-/-) mice also display reduced CGRP immunoreactivity 3 days after rhizotomy, but by postsurgical day 28 significant increases in the density of CGRP-positive axons are observed in the injured dorsal horns of these mice. Interestingly, NGF/p75(-/-) mice displayed significantly more new axonal growth when compared to NGF transgenic mice expressing full-length p75NTR. Immunohistochemical and ultrastructural analyses revealed that this axonal growth is not the result of regeneration but rather injury-induced sprouting by intact DRG central processes into the lesion site. This collateral growth is restricted to deafferentated areas of the dorsal horn, and we therefore propose that this is an example of compensatory sprouting by NGF-sensitive axons in the spinal cord, a response that is enhanced in the absence of NGF binding to p75NTR.

Animals↗
PubMed1991

Two systems of branching axons in monkey's retina.

Several monkey retinae were stained, by using the reduced silver technique, in order to analyse long-distance intraretinal connections. Long, bifurcating processes covering very large areas were identified. Morphological investigation of these processes suggest that they are members of two different systems of branching axons. The first population of these processes originates as axon collaterals from cell in the ganglion cell layer. These cells have a relatively large, elongated soma and straight, sparsely branching dendrites, stratified in the vitreal half of the inner plexiform layer. The main axon (0.6 microns average diameter) passes along the optic fibre bundles, disappearing into the optic disk, whilst its collaterals run mainly in the inner plexiform layer. A cell showing similar morphology has also been found in the ganglion cell layer of a cat retina. The second population of processes consists of very thick fibres (2.1 microns average diameter) apparently originating from the optic disk. The main branches run in the space between the optic fibre layer and the ganglion cell layer, with short, secondary processes crossing the ganglion cel layer orthogonally. Many higher-order processes originate from the second-order branches; these run almost horizontally in the inner plexiform layer. The ganglion cells generating axon collaterals may constitute an intraretinal firing synchronization system, or they may be a residual feature of retinal development. The centrifugal fibres may be related to the sensitivity control during retinal dark adaptation.

Animals↗
PubMed1993

Pressure distribution at the knee joint. Influence of varus and valgus deviation without and with ligament dissection.

Traumata or repetitive microtraumata, malalignment with varus or valgus deviation, or chronic joint instability are discussed in the aetiology of osteoarthritis and osteochondritis dissecans of the knee. Biomechanical factors influencing the patterns of pressure distribution at the articular surface and the subchondral bone are suggested to be most important in the pathogenesis. Consequently, the patterns of pressure distribution at the femoral condyles of weight-bearing knee joints were investigated in a cadaveric biostatic model. The pressure in the articular joint space was evaluated with pressure-sensitive films of the knee in different joint positions in the coronal plane (10 degrees varus, 10 degrees valgus, and neutral position) without and with medial collateral ligament (MCL), lateral CL (LCL), MCL + anterior cruciate ligament (ACL) or LCL + ACL ligament division. Results demonstrated that the location of the contact area and the peak pressure depended on the joint position and stage of ligamentous division. Without ligament division, a maximum peak pressure was observed at the medial condyle in the neutral and varus positions. Only in the valgus position did the lateral condyle show a higher peak of pressure than the medial condyle. Ligament division of the LCL and LCL + ACL resulted in an increase of peak pressure at the medial condyle, particularly in the varus position. Division of the MCL and MCL + ACL ligament complex reduced the differences between the medial and lateral condyle. In the valgus position, the peak pressure was significantly higher at the lateral condyle. The absolute maximum peak pressure was measured in the varus position at the medial condyle after division of the LCL and ACL.(ABSTRACT TRUNCATED AT 250 WORDS)

Cadaver↗
PubMed2000

Using a criterion standard to validate the Alcohol-Related Problems Survey (ARPS): a screening measure to identify harmful and hazardous drinking in older persons.

We compared the Alcohol-Related Problems Survey (ARPS), a new screening measure targeted at harmful and hazardous drinking among older individuals, to a criterion standard (CS) among 22 persons aged 65 and older who reported consuming at least one drink of alcohol in the previous 12 months. The CS was conducted by a study physician and research assistant. It assessed risks from alcohol use, and consisted of a structured review of each subject's medical record, clinical interview, physical examination, and an interview with a collateral informant. Analyses included descriptive statistics for demographic and health characteristics, inter-rater reliability, agreement between the ARPS and the CS, reasons for disagreement, and sensitivity and specificity of the ARPS as compared to the CS. Using Landis and Koch criteria, inter-rater reliability between two physicians for 11 subjects was substantial (weighted kappa 0.79), but agreement between the ARPS and the CS was only fair (weighted kappa 0.28). Reasons for disagreement included problems with ARPS' questions and classification rules, and problems with study physicians' assessments of drinking risk. Based on these reasons for disagreement, we made revisions in the ARPS and its classification rules. Agreement between the revised ARPS and the CS improved substantially (weighted kappa 0.62). Sensitivity and specificity of the original ARPS were 80% and 50%, respectively, and both improved to 82% after revisions. The revised ARPS is sensitive and specific for identifying harmful and hazardous drinking in older persons as determined by clinicians.

Aged↗
PubMed2003

Dentate granule cell GABA(A) receptors in epileptic hippocampus: enhanced synaptic efficacy and altered pharmacology.

The dentate gyrus (DG) normally functions as a filter, preventing propagation of synchronized activity into the seizure-prone hippocampus. This filter or 'gatekeeper' attribute of the DG is compromised in various pathological states, including temporal lobe epilepsy (TLE). This study examines the role that altered inhibition may play in the deterioration of this crucial DG function. Using the pilocarpine animal model of TLE, we demonstrate that inhibitory synaptic function is altered in principal cells of the DG. Spontaneous miniature inhibitory postsynaptic currents (mIPSCs) recorded in dentate granule cells (DGCs) from epileptic animals were larger, more sensitive to blockade by zinc and less sensitive to augmentation by the benzodiazepine type site 1 modulator zolpidem. Furthermore, mIPSCs examined during a quiescent period following injury but preceding onset of epilepsy were significantly smaller than those present either in control or in TLE DGCs, and had already acquired sensitivity to blockade by zinc prior to the onset of spontaneous seizures. Rapid agonist application experiments demonstrated that prolonged (>35 ms) exposure to zinc is required to block GABAA receptors (GABAARs) in patches pulled from epileptic DGCs. Therefore, zinc must be tonically present to block DGC GABAARs and alter DG function. This would occur only during repetitive activation of mossy fibres. Thus, in the pilocarpine animal model of TLE, an early, de novo, expression of zinc-sensitive GABAARs is coupled with delayed, epilepsy-induced development of a zinc delivery system provided by aberrant sprouting of zinc-containing mossy fibre recurrent collaterals. The temporal and spatial juxtaposition of these pathophysiological alterations may compromise normal 'gatekeeper' function of the DG through dynamic zinc-induced failure of inhibition, predisposing the hippocampal circuit to generate seizures.

Animals↗
PubMed1993

Epigenetic mechanisms of drug resistance: drug-induced DNA hypermethylation and drug resistance.

In a model system employing Chinese hamster V-79 cells, the DNA synthesis inhibitor 3'-azido-3'-deoxythymidine (BW A509U, AZT) was shown to induce genome-wide DNA hypermethylation, low-frequency silencing of thymidine kinase (TK; EC 2.7.1.21) gene expression, and resistance to AZT. Twenty-four hours of exposure of V-79 cells to 150 microM AZT led to > 2-fold enhancement of genomic 5-methylcytosine levels and produced TK- epimutants at a rate approximately 43-fold above background. Such AZT-induced TK- epimutants were shown to be severely reduced in their capacity to activate AZT to its proximate antiviral form, AZT 5'-monophosphate, as compared with the TK+ parental cell line from which they were derived. TK- clones isolated under these conditions were shown to be 9- to 24-fold more resistant to the cytotoxic effects of AZT than the parental TK+ cell line and showed collateral resistance to 5-fluoro-2'-deoxyuridine. Three of four TK- epimutants could be reactivated at very high frequency (8-73%) to the TK+ AZT-sensitive phenotype by 24 hr of exposure to the demethylating agent 5-azadeoxycytidine (5-azadC), implying that drug-induced DNA hypermethylation, rather than classical mutation, was involved in the original gene-silencing event in these three clones. These 5-azadC-induced TK+ revertants concomitantly regained the ability to metabolize AZT to its 5'-monophosphate. RNA slot blot analyses indicated that the four AZT-induced TK- clones expressed 8.9%, 15.6%, 17.8%, and 11.1% of the parental level of TK mRNA. The three clones that were reactivatable by 5-azadC showed reexpression of TK mRNA to levels 84.4%, 51.1%, and 80.0% that of the TK+ parental cell line. These experiments show that one potential mechanism of drug resistance involves drug-induced DNA hypermethylation and resulting transcriptional inactivation of cellular genes whose products are required for drug activation.

Animals↗
PubMed1996

Magnetic resonance imaging of the musculoskeletal system. Part 4. The knee.

Since its introduction to musculoskeletal imaging in the early 1980s, magnetic resonance imaging has proven to be an excellent technique for evaluating patients with knee problems. Studies have shown it to be accurate in the identification of abnormalities of the menisci, ligaments, patellofemoral joints, and other soft tissue and osseous structures in the knee. The main advantages of magnetic resonance imaging are its noninvasive nature and its high accuracy and negative predictive value in evaluating the menisci and anterior cruciate ligament. Magnetic resonance imaging has been shown to be useful in the detection and diagnosis of various traumatic and nontraumatic knee abnormalities. It has also proved useful in the diagnosis of occult or unsuspected bone lesions. Magnetic resonance imaging can therefore help in the selection of those patients who need therapeutic arthroscopy. There is evidence that magnetic resonance imaging of the knee is a cost effective screening technique when used in conjunction with the clinical findings in patients who are candidates for arthroscopy. Magnetic resonance imaging of the knee is still a relatively expensive modality.

Anterior Cruciate Ligament Injuries↗
PubMed1988

MR imaging of portal vein thrombosis.

MR imaging is emerging as a potential means of detecting portal venous thrombosis (PVT). Therefore, we attempted to establish specific criteria with which to diagnose PVT on conventional spin-echo images. In a retrospective review of 342 consecutive abdominal MR scans performed with a 0.5-T magnet, we identified nine patients with persistent signal in the portal vein and used the findings in these patients to establish criteria with which to diagnose PVT. We subsequently applied these criteria to 109 additional consecutive abdominal MR scans performed with the same magnet. Fifteen cases were found in which all images showed either (1) signal involving the entire width of the portal vein lumen, which approximated (with T1 weighting) and exceeded (with T2 weighting) the intensity of the hepatic parenchyma in images in which the hepatic veins showed a complete flow void or (2) complete nonvisualization of the portal vein and its major branches in images that showed a flow void in portal venous collaterals and hepatic veins. All patients had unequivocal findings of PVT on at least one other imaging study (CT or sonography) or at surgery. Although the sensitivity of these signs could not be calculated, their specificity was 100%. We conclude that in the presence of these signs, the diagnosis of PVT can be made with confidence.

Adolescent↗
PubMed2002

Relationship between findings of conventional and contrast-enhanced transcranial color-coded real-time sonography and angiography in patients with basilar artery occlusion.

BACKGROUND AND PURPOSE: Contrast-enhanced transcranial color-coded real-time sonography (TCCS) is a promising tool for the evaluation of brain circulation. The purpose of the present study was to assess the diagnostic ability of conventional and contrast-enhanced TCCS in patients with acute stroke and basilar artery occlusion and to compare the findings with those of angiography. METHODS: We prospectively performed conventional and contrast-enhanced TCCS within 3 days before or after digital subtraction angiography or MR angiography in 62 consecutive patients with acute ischemic stroke. We assigned the patients to two groups on the basis of angiographic findings: basilar artery occlusion group (n = 7) and control group without basilar artery occlusion (n = 55). We obtained basilar artery flow images showing the direction of blood flow using TCCS through a suboccipital window. RESULTS: In the control group, the detection rate of basilar artery flow using conventional and contrast-enhanced TCCS was 76.4% and 98.2%, respectively (P <.001), and the flow direction was antegrade in all patients. In the basilar artery occlusion group, neither conventional nor contrast-enhanced TCCS could obtain flow images of the proximal basilar artery in any patient. In five patients with proximal basilar artery occlusion, a reversed flow image in the distal basilar artery obtained by contrast-enhanced TCCS was confirmed by angiography to be blood supply through collateral circulation from the carotid systems. However, two patients with distal basilar artery occlusion did not have this sign. CONCLUSION: Contrast-enhanced TCCS is more sensitive in imaging basilar artery flow than is conventional TCCS. When examined with contrast-enhanced TCCS, a combination of absent basilar artery flow and the reversed basilar artery flow sign may be a diagnostic indicator of basilar artery occlusion.

Aged↗
PubMed2002

[Measuring perfusion and diffusion in neuroradiology].

Neuroradiology should be regarded as a discipline with a strong focus on integral diagnosis of morphology and function of the central nervous system. With perfusion magnetic resonance imaging (P-MRI) and diffusion-weighted magnetic resonance imaging (DWI) the functional micro-structural analysis of the central nervous system has been made possible. So, disease processes may be characterised on a molecular level and P-MRI as well as DWI are now integrated in clinical routine diagnosis to improve therapy planning.

Brain↗