Comparison of magnetic resonance volume flow rates, angiography, and carotid Dopplers. Preliminary results

BACKGROUND AND PURPOSE: We compared the results of conventional angiography, carotid Doppler, and magnetic resonance angiography volume flow rates to determine the clinical utility of volume flow rate assessment of blood flow to the anterior circulation in patients with carotid occlusive disease. METHODS: From 11 symptomatic patients, a total of 22 extracranial carotid arteries were studied with all three techniques. The studies were independently read, and regression analysis was used to compare the measurements. RESULTS: Carotid Doppler measurements of the distal extracranial carotid arteries were proportional to the inverse of the extracranial carotid volume flow rate (r = .53, R2 = 29%, P < .01), volume flow rates were proportional to the inverse of measured percent stenosis on angiography (r = .84, R2 = 71%, P < .01), and Dopplers were proportional to angiography (r = .94, R2 = 90%, P < .01). Symptomatic Doppler systolic velocity was significantly higher (P < .002), symptomatic measured stenosis was significantly higher (P < .002), and symptomatic volume flow rate was significantly lower (P < .01) than their respective asymptomatic-side values. These preliminary observations, however, may well change once a large data set, especially one in which more patients with high-grade carotid stenosis are included, is studied. CONCLUSIONS: Assessment of carotid volume flow rates by magnetic resonance angiography quantifies flow reduction secondary to atherosclerotic occlusive disease. The easily obtained flow data add both documentation of arterial flow characteristics related to internal carotid stenosis and information regarding the adequacy of collateral pathways.     

Identification of potent P2Y-purinoceptor agonists that are derivatives of adenosine 5'-monophosphate

1. A series of chain-extended 2-thioether derivatives of adenosine monophosphate were synthesized and tested as agonists for activation of the phospholipase C-linked P2Y-purinoceptor of turkey erythrocyte membranes, the adenylyl cyclase-linked P2Y-purinoceptor of C6 rat glioma cells, and the cloned human P2U-receptor stably expressed in 1321N1 human astrocytoma cells. 2. Although adenosine monophosphate itself was not an agonist in the two P2Y-purinoceptor test systems, eleven different 2-thioether-substituted adenosine monophosphate analogues were full agonists. The most potent of these agonists, 2-hexylthio AMP, exhibited an EC50 value of 0.2 nM for activation of the C6 cell receptor. This potency was 16,000 fold greater than that of ATP and was only 10 fold less than the potency of 2-hexylthio ATP in the same system. 2-hexylthio adenosine was inactive. 3. Monophosphate analogues that were the most potent activators of the C6 cell P2Y-purinoceptor were also the most potent activators of the turkey erythrocyte P2Y-purinoceptor. However, agonists were in general more potent at the C6 cell receptor, and potency differences varied between 10 fold and 300 fold between the two receptors. 4. Although 2-thioether derivatives of adenosine monophosphate were potent P2Y-purinoceptor agonists no effect of these analogues on the human P2U-purinoceptor were observed. 5. These results support the view that a single monophosphate is sufficient and necessary for full agonist activity at P2Y-purinoceptors, and provide insight for strategies for development of novel P2Y-purinoceptor agonists of high potency and selectivity.     

Angiotensin II receptor type 1 mRNA is upregulated in atria of patients with end-stage heart failure

There is increasing evidence that pathological changes in the myocardium during chronic heart failure (CHF) are partly regulated through the activation of the renin-angiotensin system (RAS), an effect mediated by the angiotensin II type 1 receptor (AT1R). We examined the expression of cardiac AT1R mRNA in normal (atria, n=7; ventricle, n=3) and end-stage CHF human hearts (atria, n=8; ventricle, n=14). Tissue was snap-frozen immediately after explantation during orthotopic cardiac transplantation; control specimens were obtained from healthy donor hearts rejected for technical reasons. Northern blots of purified total mRNA from each tissue were hybridized with a random primed radiolabeled probe for the coding sequence of AT1R. Stringent conditions were used for both hybridization (5X SSC, 65 degrees C) and washing (0.5X SSC, 0.1% SDS, 65 degrees C) of the membrane. Left and right atrial tissue showed low levels of AT1R mRNA expression in the controls, with statistically significant upregulation of expression in tissue from pathological hearts; CHF atria 1.28+/-0.86 optical density (OD) units, control atria 0.56+/-0.31 OD units, P=0.05 (mean+/-s.d.). There were undetectable levels in ventricles from either control (2/2) or dilated hearts (7/7). The results were independent of the etiology of the heart failure and suggest that increased levels of atrial AT1R mRNA may occur in response to elevated atrial pressures in heart failure.     

Predicting oxide stability in high-temperature water vapor

The importance of understanding and predicting the interactions of oxides with water vapor at high temperatures is demonstrated in this article. Methods for observing volatilization phenomena and identifying the chemical formulae for volatile metal hydroxides are discussed. In addition, techniques for obtaining accurate thermodynamic data for gaseous metal hydroxide species are described. Detailed examples of the stability of the principle structural and/or protective oxides chromia (Cr₂O₃), silica (SiO₂), and alumina (Al₂O₃) in high-temperature water vapor are included.     

X-linked juvenile retinoschisis: localization between (DXS1195, DXS418) and AFM291wf5 on a single YAC

We studied 17 pedigrees with 108 affected males with X-linked juvenile retinoschisis (RS; McKusick No. 31270) and have analyzed all of the known polymorphic markers in the RS region of Xp22.1-p22.2 between DXS987 and DXS41. By haplotype analyses we found 7 individuals who showed crossovers in this interval surrounding RS. We previously reported AFM291wf5 as the centromeric boundary, and this remains unchanged in the present study. A new recombination was identified on the telomeric side at (DXS1195, DXS418). Our data support the locus order Xpter--(DXS987, DXS207, DXS1053, DXS43)--(DXS1195, DXS418)--(RS, DXS257, DXS999)--(AFM291wf5, DXS443)--DXS1052--(DXS1226, DXS274, DXS41)--Xcen; loci grouped in parentheses could not be mutually ordered by our genetic data. Physical mapping has indicated a distance of at most 900-1,000 kb between (DXS1195, DXS418) and AFM291wf5. No recombination was observed between RS and DXS257 which lies in our new interval of interest, but one critical individual was not informative with this marker. Our data now define the smallest RS inclusion interval. This interval is contained on a single YAC from which we have identified expressed sequences as candidate genes for RS.     

Physiological and morphological heterogeneity of dentate gyrus-hilus interneurons in the gerbil hippocampus in vivo

A variety of morphological types of dentate gyrus/hilus interneurons have been described, but little is known about their corresponding physiological characteristics. To address this issue, intracellular responses to current injection and perforant path stimulation were obtained from putative dentate interneurons in anaesthetized adult gerbils. Our sample of interneurons showed heterogeneity in their intrinsic physiological characteristics and spike thresholds to perforant path stimulation, suggesting the existence of distinct physiologically-defined classes. 'Fast-spiking' interneurons had a low threshold to perforant path stimulation, whereas 'slow-spiking' interneurons responded with predominantly inhibitory potentials. In several cases, cells were intracellularly labelled with biocytin for visualization. Interneurons with different physiological traits had distinct morphological features. These results confirm that, as in hippocampus proper, morphologically identifiable interneurons in the dentate hilus show electrophysiological features that are likely to reflect functionally specific roles in informational processing.     

Rates of reinfection with Echinococcus granulosus, Taenia hydatigena, taenia ovis and other cestodes in a rural dog population in Uruguay

Forced thinking is an incompletely understood and rarely described epileptic aura. We studied three patients with forced thinking from left frontal lesions, two neoplastic and one vascular. All three experienced repetitive, intrusive thoughts at the onset of seizures. Their forced thinking was associated with the desire to vocalize, orobuccal movements, and speech arrest. The episodes occurred with other ictal manifestations and responded to antiseizure therapy. These patients suggest that epileptic forced thinking is a heterogeneous phenomenon; forced thinking from left frontal lesions is a manifestation of expressive language and is distinct from experiential thoughts arising from temporal limbic foci.     

Phenotypic analysis of antigen-specific T lymphocytes

Identification and characterization of antigen-specific T lymphocytes during the course of an immune response is tedious and indirect. To address this problem, the peptide-major histocompatability complex (MHC) ligand for a given population of T cells was multimerized to make soluble peptide-MHC tetramers. Tetramers of human lymphocyte antigen A2 that were complexed with two different human immunodeficiency virus (HIV)-derived peptides or with a peptide derived from influenza A matrix protein bound to peptide-specific cytotoxic T cells in vitro and to T cells from the blood of HIV-infected individuals. In general, tetramer binding correlated well with cytotoxicity assays. This approach should be useful in the analysis of T cells specific for infectious agents, tumors, and autoantigens.